TY - JOUR. T1 - Establishment of a Kit-negative cell line of melanocyte precursors from mouse neural crest cells. AU - Kawa, Yoko. AU - Soma, Yoshinao. AU - Nakamura, Masayuki. AU - Ito, Masaru. AU - Kawakami, Tamihiro. AU - Baba, Takako. AU - Sibahara, Kuniko. AU - Ohsumi, Kayoko. AU - Ooka, Shiho. AU - Watabe, Hidenori. AU - Ono, Hirotake. AU - Hosaka, Eri. AU - Kimura, Satoko. AU - Kushimoto, Tsuneto. AU - Mizoguchi, Masako. PY - 2005/6. Y1 - 2005/6. N2 - We previously established a mouse neural crest cell line named NCCmelb4, which is positive for Kit and negative for tyrosinase. NCCmelb4 cells were useful to study the effects of extrinsic factors such as retinoic acids and vitamin D3 on melanocyte differentiation, but in order to study the development of melanocytes from multipotent neural crest cells, cell lines of melanocyte progenitors in earlier developmental stages are needed. In the present study, we established an immortal cell line named NCC-melb4M5 that was derived from NCCmelb4 ...
Within the hindbrain region, neural crest cell migration is organized into three streams that follow the segmentation of the neuroepithelium into distinct rhombomeric compartments. Although the streaming of neural crest cells is known to involve signals derived from the neuroepithelium, the molecular properties underlying this process are poorly understood. Here, we have mapped the expression of the signaling component of two secreted class III Semaphorins, Semaphorin (Sema) 3A and Sema 3F, at time points that correspond to neural crest cell migration within the hindbrain region of the chick. Both Semaphorins are expressed within rhombomeres at levels adjacent to crest-free mesenchyme and expression of the receptor components essential for Semaphorin activity by neural crest cells suggests a function in restricting neural crest cell migration. By using bead implantation and electroporation in ovo, we define a role for both Semaphorins in the maintenance of neural crest cell streams in proximity to the
Greiner, Johannes, Hauser, Stefan, Widera, Darius, Qunneis, Firas, Müller, Janine, Zander, Christin, Martin, Ina, Mallah, Jana, Prante, Christian, Schwarze, Hartmut, Prohaska, Wolfgang, Beyer, André, Rott, Karsten, Hütten, Andreas, Gölzhäuser, Armin, Sudhoff, Holger, Kaltschmidt, Christian, and Kaltschmidt, Barbara. Efficient animal-serum free 3D cultivation method for adult human neural crest-derived stem cell therapeutics. European Cells & Materials 22 (2011): 403-419 ...
Our data implicate Disc1 in the transcriptional repression of foxd3 and sox10, two transcription factors that are crucial for multiple steps of CNC development. Evidence points to a role for Foxd3 as a transcriptional repressor crucial for the maintenance of neural crest progenitor pools, neural crest migration and the differentiation of some neural crest derivatives (Cheung et al., 2005; Lister et al., 2006; Montero-Balaguer et al., 2006; Stewart et al., 2006; Teng et al., 2008). Zebrafish foxd3 mutants have normal numbers of premigratory neural crest, but delayed neural crest migration and depletion of certain neural crest derivatives (Lister et al., 2006; Stewart et al., 2006). Interestingly, the only neural crest derivative with foxd3 expression during and after terminal differentiation is peripheral glia (Kelsh et al., 2000), indicating a possible role for this transcription factor in the differentiation of this derivative. Similar to the Disc1 morphants reported here, colgate (hdac1) ...
TY - JOUR. T1 - Neural crest cell differentiation and carcinogenesis. T2 - Capability of goldfish erythrophoroma cells for multiple differentiation and clonal polymorphism in their melanogenic variants. AU - Matsumoto, Jiro. AU - Wada, Kumiko. AU - Akiyama, Toyoko. PY - 1989/5. Y1 - 1989/5. N2 - Multiple differentiation shown by a single cell line (GEM 81) of goldfish erythrophoroma (tumors of integumental erythrophores) cells after administration of chemical induction in vitro includes 1) melanogenesis, 2) formation of reflecting platelets, 3) synthesis of pteridines heterogeneous to this species, 4) formation of dermal skeletons such as teeth and fin rays, 5) production of neuronal characters, and 6) genesis of lentoid bodies. Melanogenic cells, highest in inducibility, also show remarkable phenotypic diversification in their cell morphology, pigmentation, and physiologic response. In this paper, the following findings are presented; a) multiple differentiation shown by erythrophoroma cells ...
Pinch1, an adaptor protein composed of 5 LIM domains, has been suggested to play an important role in multiple cellular processes. We found that Pinch1 is highly expressed in neural crest cells and their derivatives. To examine the requirement for Pinch1 in neural crest development, we generated neural crest conditional Pinch1 knockout mice using the Wnt1-Cre/loxP system. Neural crest conditional Pinch1 mutant embryos die perinatally from severe cardiovascular defects with an unusual aneurysmal common arterial trunk. Pinch1 mutants also exhibit multiple deficiencies in cranial neural crest-derived structures. Fate mapping demonstrated that initial migration of neural crest cells to the pharyngeal arch region occurs normally in the mutant embryos. However, in the cardiac outflow tract of mutants, neural crest cells exhibited hyperplasia and failed to differentiate into smooth muscle. Markedly increased apoptosis is observed in outflow tract cushions of mutants between embryonic days 11.5 and 13.5, likely
The proposed pathways of chick cranial neural crest migration and their relationship to the rhombomeres of the hindbrain have been somewhat controversial, with differing results emerging from grafting and DiI-labelling analyses. To resolve this discrepancy, we have examined cranial neural crest migratory pathways using the combination of neurofilament immunocytochemistry, which recognizes early hindbrain neural crest cells, and labelling with the vital dye, DiI. Neurofilament-positive cells with the appearance of premigratory and early-migrating neural crest cells were noted at all axial levels of the hindbrain. At slightly later stages, neural crest cell migration in this region appeared segmented, with no neural crest cells obvious in the mesenchyme lateral to rhombomere 3 (r3) and between the neural tube and the otic vesicle lateral to r5. Focal injections of DiI at the levels of r3 and r5 demonstrated that both of these rhombomeres generated neural crest cells. The segmental distribution of ...
Neural crest cells (NCCs) are a multipotent, migratory cell population that generates an astonishingly diverse array of cell types during vertebrate development. The trunk neural crest has long been considered of particular significance. First, it has been held that the trunk neural crest has a morphogenetic role, acting to coordinate the development of the peripheral nervous system, secretory cells of the endocrine system and pigment cells of the skin. Second, the trunk neural crest additionally has skeletal potential. However, it has been demonstrated that a key role of the trunk neural crest streams is to organize the innervation of the intestine. Although trunk NCCs have a limited capacity for self-renewal, sometimes they become neural-crest-derived tumor cells and reveal the fact that that NCCs and tumor cells share the same molecular machinery. In this review we describe the routes taken by trunk NCCs and consider the signals and cues that pattern these trajectories. We also discuss recent
Because of its unique ability to generate a wide variety of both neural and nonneural derivatives, the neural crest is an ideal model system to study the factors regulating cell lineage decisions in stem and progenitor cells. The use of various cell culture techniques and in vivo functional assays, including cell type-specific gene manipulation in mouse, helped to identify signaling factors involved in this process. Moreover, it became apparent that the biological functions of growth factors acting on neural crest cells depend on the context provided by the extracellular microenvironment. Thus, signaling molecules have to be viewed as parts of complex networks that change with time and location. Neural crest cells have to integrate these signals to ensure the generation of appropriate numbers of differentiating progeny. It will be important to determine how such signaling networks are established and how they elicit multiple signaling responses in neural crest cells to activate appropriate ...
The neural crest is a multipotent cell population that migrates from the dorsal edge of the neural tube to various parts of the embryo where it differentiates into a remarkable variety of different cell types. Initial induction of neural crest is mediated by a combination of BMP, Wnt, FGF, Retinoic acid and Notch/Delta signaling. The two-signal model for neural crest induction suggests that BMP signaling induces the competence to become neural crest. The second signal involves Wnt acting through the canonical pathway and leads to expression of neural crest markers such as slug. Wnt signals from the neural plate, non-neural ectoderm and paraxial mesoderm have all been suggested to play a role in neural crest induction. We show that Xenopus frizzled7 (Xfz7) is expressed in the dorsal ectoderm including early neural crest progenitors and is a key mediator of the Wnt inductive signal. We demonstrate that Xfz7 expression is induced in response to a BMP antagonist, noggin, and that Xfz7 can induce ...
Neural crest cells are a group of temporary, multipotent (can give rise to some other types of cells but not all) cells that are pinched off during the formation of the neural tube (precursor to the spinal cord and brain) and therefore are found at the dorsal (top) region of the neural tube during development. They are derived from the ectoderm germ layer, but are sometimes called the fourth germ layer because they are so important and give rise to so many other types of cells. They migrate throughout the body and create a large number of differentiated cells such as neurons, glial cells, pigment-containing cells in skin, skeletal tissue cells in the head, and many more. Cardiac neural crest cells (CNCCs) are a type of neural crest cells that migrate to the circumpharyngeal ridge (an arc-shape ridge above the pharyngeal arches) and then into the 3rd, 4th and 6th pharyngeal arches and the cardiac outflow tract (OFT). They extend from the otic placodes (the structure in developing embryos that ...
TY - JOUR. T1 - Evidence for a novel enzymatic mechanism of neural crest cell migration on extracellular glycoconjugate matrices. AU - Runyan, R. B.. AU - Maxwell, G. D.. AU - Shur, B. D.. PY - 1986. Y1 - 1986. N2 - Migrating embryonic cells have high levels of cell surface galactosyltransferase (GalTase) activity. It has been proposed that GalTase participates during migration by recognising and binding to terminal N-acetylglucosamine (GlcNAc) residues on glycoconjugates within the extracellular matrix (Shur, B.D., 1982, Dev. Biol. 91:149-162). We tested this hypothesis using migrating neural crest cells as an in vitro model system. Cell surface GalTase activity was perturbed using three independent sets of reagents, and the effects on cell migration were analyzed by time-lapse micorphotography. The GalTase modifier protein, alpha-lactalbumin (α-LA), was used to inhibit surface GalTase binding to terminal GlcNAc residues in the underlying substrate. α-LA inhibited neural crest cell migration ...
Neural crest cells were transplanted from one position in the body to another position. They developed into neural crest derivates from their new position. Neural crest cells are apparently pluripotent, as they give rise to the cell types expected from the position to which they have been transplanted.. For example, any neural crest cell can give rise to parasympathetic ganglia if transplanted to a certain position. Thus, neural crest cells must respond to environmental cues during their migration and subsequent differentiation. These environmental cues are often identical to the cues used by axons. ...
Neural crest cells are both highly migratory and significant to vertebrate organogenesis. However, the signals that regulate neural crest cell migration remain unclear. In this study, we test the function of differential screening-selected gene aberrant in neuroblastoma (DAN), a bone morphogenetic protein (BMP) antagonist we detected by analysis of the chick cranial mesoderm. Our analysis shows that, before neural crest cell exit from the hindbrain, DAN is expressed in the mesoderm, and then it becomes absent along cell migratory pathways. Cranial neural crest and metastatic melanoma cells avoid DAN protein stripes in vitro. Addition of DAN reduces the speed of migrating cells in vivo and in vitro, respectively. In vivo loss of function of DAN results in enhanced neural crest cell migration by increasing speed and directionality. Computer model simulations support the hypothesis that DAN restrains cell migration by regulating cell speed. Collectively, our results identify DAN as a novel factor ...
By analyzing the hearts of quail-chick chimeras, it was found that neural crest cells at the level of occipital somites 1 to 3 migrate to the region of the aorticopulmonary septum. Bilateral removal of this neural crest population prior to migration causes malformation of the aorticopulmonary septum resulting in common arterial outflow channels or transposition of the great vessels. ...
foxd3 encodes a winged helix/forkhead class transcription factor expressed in the premigratory neural crest cells of many vertebrates. We have investigated the function of this gene in zebrafish neural crest by a loss of function approach using antisense morpholino oligonucleotides and immunostaining for Foxd3 protein. Knockdown of Foxd3 expression produces deficits in several differentiated neural crest derivatives, including jaw cartilage, peripheral neurons, and glia, and iridophore pigment cells. Other derivatives, such as melanophore and xanthophore pigment cells are not affected. Reduction in the expression of several lineage-specific markers becomes evident soon after the onset of neural crest migration, suggesting that Foxd3 knockdown affects these lineages at early stages in their development. In contrast, analysis of the expression of early neural crest markers indicates little effect on neural crest induction or initial emigration. Finally, cell transplantation suggests that with ...
Trunk neural crest migration in the zebrafish is confined to the centre of the medial surface of each somite and the pattern of migration is determined before neural crest cells contacts the sclerotome cells. Unlike other animals such as mice and birds, the sclerotome only makes up an inconsequential part of the somites in zebrafish and did not disrupt neural crest migration and DRG development[84]. It has been demonstrated that the myotome of the zebrafish contributes more in the establishment of neural crest cell migration patterns together with neural crest cells[85]. In particular, the adaxial cells, the first cells to develop and migrate from the myotome, helps in the regulation of trunk neural crest migration patterns. These slow muscle precursors have been shown to be crucial for normal migration patterns as their removal resulted in the accumulation of trunk neural crest cells at the level of the notochord[86]. Another key aspect in the proper development of DRG neurons in zebrafish lies ...
Our data show that knockout of the arginyltransferase Ate1 in the cells of the neural crest lineage results in multiple morphogenic defects and perinatal lethality in mice. It has been previously shown that complete Ate1 knockout in mice leads to embryonic lethality and defects in cardiovascular development and angiogenesis [9] that are reminiscent of the defects seen in mouse models with knockout of genes implicated in cell adhesion and migration during embryogenesis [10]. Here we show for the first time that Ate1 deletion in the migratory subpopulations of the neural crest cells leads to delayed development and reduced size of the neural crest-derived organs and tissues, suggesting that Ate1-dependent migration of the neural crest cells is essential for normal embryogenesis.. We have previously shown that Ate1 knockout embryonic fibroblasts have leading edge defects that arise from abnormalities in the non-arginylated actin cytoskeleton [24]. Here we found that in addition to the abnormal ...
Neural crest cells are a group of multipotent stem cell that migrate to various locations and give rise to many diverse cell types in the vertebrate body. The ENS arises from vagal neural crest stem cells that originate from the post-otic dorsal neural tube. Vagal neural crest cells are multipotent and can give rise to the outflow tract of the heart, enteric ganglia, sympathetic ganglia, as well as pigment cells of the skin. To become enteric ganglia during development, vagal neural crest migrate ventrally from the neural tube and enter the primitive foregut tissue. They then migrate along the rostrocaudal extent of the gut in response to microenvironmental signaling cues to until they eventually reach the hindgut. These enteric neural crest cells (ENC) eventually give rise to a diverse array of neurons and glia that form the enteric ganglia ...
Massachusetts General Hospital and Harvard Medical School Purpose: Vertebrate neural crest development depends on pluripotent, migratory neural crest (NC) cells. Isolation and culture of zebrafish NC cells has not been previously reported. In vitro culture of NC cells allows evaluation of in vivo findings in a more controlled environment. Here we report for the first time the isolation, in vitro culture and characterization of NC cells from zebrafish embryos. We apply the NC culture to determine if these cells possess stem cell or progenitor cell properties of multi-lineage differentiation, maintenance and renewal.. Methods: NC cells were isolated from transgenic sox10::egfp embryos using FACS and cultured in a complex proliferation medium, on substrates coated with extra cellular matrix proteins, with growth factors to induce differentiation into various lineages. NC multi-lineage differentiation was determined by immunocytochemistry and RT-PCR, cell migration was assessed by wound healing ...
Neural Crest Cell Emigration and Migration Neural crest cells are among the most migratory cell type in vertebrate embryos. We are characterizing the machinery responsible for neural crest cell movement, the nature of the neural crest epithelial to mesenchymal transition to form a migratory cell type and the role of the migratory environment in influencing migratory pathway choices. A variety of cell labeling techniques, including DiI-labeling, microsurgical grafts and confocal time-lapse microscopy, are used to follow the pathways of neural crest migration in in a number of vertebrate species. ...
Purpose: : Long thin sympathetic axons transport tissue plasminogen activator(t-PA) to the eye. There it is released in response to adrenergic stimulations. The t-PA is synthesized and packaged in transport vesicles in superior cervical sympathetic ganglion neuron cell bodies(1) .Plasmin activated by t-PA has long been thought to accelerate the trabecular outflow of aqueous humor. Our purpose here is to map the neural crest origins of cells able to produce t-PA within the eye. Methods: : A promoter mouse line- whose human t-PA Cre transgene is specifically expressed by sympathetic nerves and all other crest derivatives(2)- was crossed with a Lac Z reporter expressing the enhanced green fluorescent protein(EGFP) transgene. PCR sorted pups showed both t-PA promoter and EGFP expressions confined within crest-derived cells. Cryosections were viewed by confocal and UV microscopy ,and immunostained for t-PA antigen.Cultured human uveal melanocytes were stimlated with phenylephrine to confirm a t-PA ...
The neural crest is an embryonic stem cell population whose migratory behaviour has been likened to malignant invasion. The neural crest, as does cancer, undergoes an epithelial-to-mesenchymal transition and migrates to colonize almost all the tissues of the embryo. Neural crest cells exhibit collective cell migration, moving in streams of high directionality. The migratory neural crest streams are kept in shape by the presence of negative signals in their vicinity. The directionality of the migrating neural crest is achieved by contact-dependent cell polarization, in a phenomenon called contact inhibition of locomotion. Two cells experiencing contact inhibition of locomotion move away from each other after collision. However, if the cell density is high only cells exposed to a free edge can migrate away from the cluster leading to the directional migration of the whole group. Recent work performed in chicks, zebrafish and frogs has shown that the non-canonical Wnt-PCP (planar cell polarity) ...
Analysis of early human neural crest development[5] The outstanding migration and differentiation capacities of neural crest cells (NCCs) have fascinated scientists since Wilhelm His described this cell population in 1868. Today, after intense research using vertebrate model organisms, we have gained considerable knowledge regarding the origin, migration and differentiation of NCCs. However, our understanding of NCC development in human embryos remains largely uncharacterized, despite the role the neural crest plays in several human pathologies. Here, we report for the first time the expression of a battery of molecular markers before, during, or following NCC migration in human embryos from Carnegie Stages (CS) 12 to 18. Our work demonstrates the expression of Sox9, Sox10 and Pax3 transcription factors in premigratory NCCs, while actively migrating NCCs display the additional transcription factors Pax7 and AP-2alpha. Importantly, while HNK-1 labels few migrating NCCs, p75(NTR) labels a large ...
The neural crest is an embryonic cell population that gives rise to much of the vertebrate craniofacial skeleton, and its evolutionary origin is generally regarded as a key step in the diversification of vertebrates. Neural crest fate maps have been generated for a number of osteichthyan model systems (e.g. mouse, chick, frog and zebrafish). However, nothing is known about the fates of neural crest cells in chondrichthyans. We have developed methods for long-term lineage tracing of cell populations in early skate embryos, and we are using these methods to generate fate maps of chondrichthyan cranial and trunk neural crest cells. This work will allow us to infer primitive fates of neural crest cells in the last common ancestor of jawed vertebrates (e.g. neural crest vs. mesodermal contributions to the craniofacial skeleton and pectoral girdle, and the skeletogenic potential of trunk neural crest cells), thereby resolving a number of outstanding controversies relating to the early evolution of the ...
Coordinating the balance between progenitor self-renewal and myogenic differentiation is required for a regulated expansion of the developing muscles. Previous observation that neural crest cells (NCCs) migrate throughout the somite regions, where trunk skeletal muscles first emerge, suggests a potential role for these cells in influencing early muscle formation. However, specific signaling interactions between NCCs and skeletal muscle cells remain unknown. Here we show that mice with specific NCC and peripheral nervous system defects display impaired survival of skeletal muscle and show skeletal muscle progenitor cell (MPC) depletion due to precocious commitment to differentiation. We show that reduced NCC-derived Neuregulin1 (Nrg1) in the somite region perturbs ErbB3 signaling in uncommitted MPCs. Using a combination of explant culture experiments and genetic ablation in the mouse, we demonstrate that Nrg1 signals provided by the NCC lineage play a critical role in sustainable myogenesis, by ...
Gene regulatory network model of cranial neural crest cell (CNCC) development, adaped from PMID: 19575671. Most interactions in the model are proposed to regulate transcription of core factors involved involved in neural crest and downstream progenitor specification. Transcriptional regulation arrows are proposed to promote transcription, unless a graphical T-bar is present at the end of the arrow (commented to be inhibitors of transcriptional regulation). Additional gene information was obtained from http://www.ncbi.nlm.nih.gov/books/NBK53143 ...
During development, cell fates are often specified in noisy and dynamic three-dimensional environments, which cells must navigate through, e.g. by migration. Examples include the formation of segments of the hindbrain and the pharyngeal arches, precursors of the jaw and larynx; these are largely composed of cranial neural crest cells, arising from distinct segmental positions in the hindbrain and migrating in streams through the head. While prevailing theories suggest that premigratory neural crest cells are pluripotent, relying on their migratory environment for fate specification, some lineage tracing studies have hinted at earlier pre-specification. It remains elusive when, where, and how neural crest cells acquire fate identities and robustly migrate to correct locations despite gene expression fluctuations within each cell, and fluctuations due to environmental signals. We study these stochastic dynamics in developmental systems. Heterogeneity is critical to robust environmental responses ...
PURPOSE OF REVIEW Metastatic melanoma is the most aggressive skin cancer and despite tremendous efforts and considerable progress in clinical treatment of melanoma patients within recent years, it remains a deadly disease. Current treatments affect melanoma cells indiscriminately, while accumulating evidence suggests that melanoma might be a disease of stem cells. This review aims to summarize the important accomplishments in the field and to emphasize the common molecular and cellular mechanisms regulating self-renewal of neural crest stem cells (NCSCs) and melanoma cells. RECENT FINDINGS A growing number of publications highlight the existence of phenotypic and functional similarities between embryonic NCSCs and melanoma cells. These studies provide compelling evidence that the propagation of melanoma cells critically depends on genes instrumental in neural crest development. The example of Sox10 and Rac1 genes provides detailed illustration of how interfering with these important genes for ...
During vertebrate embryogenesis, the cranial neural crest (CNC) forms at the neural plate border and subsequently migrates and differentiates into many types of cells. The transcription factor Snai2, which is induced by canonical Wnt signaling to be expressed in the early CNC, is pivotal for CNC induction and migration in Xenopus. However, snai2 expression is silenced during CNC migration, and its roles at later developmental stages remain unclear. We generated a transgenic X. tropicalis line that expresses enhanced green fluorescent protein (eGFP) driven by the snai2 promoter/enhancer, and observed eGFP expression not only in the pre-migratory and migrating CNC, but also the differentiating CNC. This transgenic line can be used directly to detect deficiencies in CNC development at various stages, including subtle perturbation of CNC differentiation. In situ hybridization and immunohistochemistry confirm that Snai2 is re-expressed in the differentiating CNC. Using a separate transgenic Wnt reporter line
Differentiation of Neural-Crest-Derived Intermediate Pluripotent Progenitors into Committed Periodontal Populations Involves Unique Molecular Signature Changes, Cohort Shifts, and Epigenetic Modifications. Smit Jayant Dangaria, Yoshihiro Ito, Xianghong Luan, Thomas G.H. Diekwisch. Stem Cells Dev. 2011 January; 20(1): 39-52. Published online 2010 July 6. doi: 10.1089/scd.2010.0180. PMCID: PMC3128775 ...
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The human cornea contains stem cells that can be induced to express markers consistent with multipotency in cell culture; however, there have been no studies demonstrating that human corneal keratocytes are multipotent. The objective of this study is to examine the potential of human fetal keratocytes (HFKs) to differentiate into neural crest-derived tissues when challenged in an embryonic environment. HFKs were injected bilaterally into the cranial mesenchyme adjacent to the neural tube and the periocular mesenchyme in chick embryos at embryonic days 1.5 and 3, respectively. The injected keratocytes were detected by immunofluorescence using the human cell-specific marker, HuNu. HuNu-positive keratocytes injected along the neural crest pathway were localized adjacent to HNK-1-positive migratory host neural crest cells and in the cardiac cushion mesenchyme. The HuNu-positive cells transformed into neural crest derivatives such as smooth muscle in cranial blood vessels, stromal keratocytes, and ...
2Vertebrate Body Plan Group, RIKEN Center for Developmental Biology. Cephalic neural crest cells play essential roles in craniofacial development. Otx2 is a gene that plays central roles in head development and is also expressed in the cephalic neural crest cells. We have previously reported Otx2 heterozygotes exhibit a variety of craniofacial defects in C57BL/6 background, but not in CBA background (Genes Dev. 9, 2646-, 1995). Here we report (1) cis-regulatory elements that are identified by making transgenic embryos with LacZ gene as a reporter (Deve, 124, 3929, 1997), (2) components of cranial nerves and skeltons that are regulated by Otx2 and their implication in vertebrate body plan, (3) mapping of a modifier gene that is responsible for the difference of the Otx2 phenotype between C57BL/6 and CBA backgrounds.. ...
In vitro studies have shown that the phorbol ester, 12-tetradecanoylphorbol 13-acetate (TPA) induces neural crest cell differentiation into melanocytes, and stimulates proliferation and differentiation of normal melanocytes. As TPA is not a physiological agent, its action is clearly mimicking some in vivo pathway involved in these processes. An understanding of the effect of TPA on the expression of melanogenic genes will therefore provide valuable insight into the molecular mechanisms regulating melanocyte differentiation. In this study, we utilized primary cultures of neural crest cells and an immortalized melanocyte cell line (DMEL-2) which proliferates in the absence of TPA, to explore the effects of TPA on key melanogenic effectors. In neural crest cells, TPA was found to be necessary for both microphthalmia associated transcription factor (Mitf) up-regulation and for melanin synthesis. Using northern blots, we show that in DMEL-2 cells, TPA significantly increases the messenger ribonucleic acid
Combined intrinsic and extrinsic influences pattern cranial neural crest migration and pharyngeal arch morphogenesis in axolotl Journal Article ...
Definition: One of the 5 distinct and partially overlapping functional domains of the premigratory neural crest. Together with the sacral neural crest cells, they develop into the ganglia of the enteric nervous system, also known as the parasympathetic ganglia. These cells, between the head and trunk, contribute post-cranially to the heart and gut, the chromatophores (pigment cells) of the epidermis, and the majority of the neurons and glial cells of the enteric nervous system. Both vagal and sacral neural crest cells contribute to the enteric nervous system in the hindgut ...
The endothelin system is a vertebrate-specific innovation with important roles in regulating the cardiovascular system and renal and pulmonary processes, as well as the development of the vertebrate-specific neural crest cell population and its derivatives. This system is comprised of three structurally similar 21-amino acid peptides that bind and activate two G-protein coupled receptors. In 1994, knockouts of the Edn3 and Ednrb genes revealed their crucial function during development of the enteric nervous system and melanocytes, two neural-crest derivatives. Since then, human and mouse genetics, combined with cellular and developmental studies, have helped to unravel the role of this signaling pathway during development and adulthood. In this review, we will summarize the known functions of the EDN3/EDNRB pathway during neural crest development, with a specific focus on recent scientific advances, and the enteric nervous system in normal and pathological conditions.
We used the chick embryo transplant model to study the reprogramming of human metastatic melanoma cells towards a benign cell type. We had previously reported that human patient-derived C8161 metastatic melanoma cells upregulated a marker of melanin synthesis, Mart-1, after exposure to unknown signals in the embryonic neural crest microenvironment (Kulesa et al., 2006). The goal of this study was to identify and examine the function of the microenvironmental signal(s) underlying the reprogramming process. To enable the dynamic readout of one of the changes in metastatic melanoma cell state, we generated a lentiviral Mart-1:GFP reporter and methodically determined the age, tissue type and ultimately the factor that induced re-expression of Mart-1. We learned that the neurotrophin NGF induced Mart-1 re-expression and changes in cell behavior and gene expression of human C8161 metastatic melanoma cells. We confirmed Mart-1:GFP re-expression in C8161 cells after NGF exposure using Mart-1 antibody ...
TY - JOUR. T1 - Pak1ip1 Loss-of-Function Leads to Cell Cycle Arrest, Loss of Neural Crest Cells, and Craniofacial Abnormalities. AU - Panoutsopoulos, Alexios A.. AU - De Crescenzo, Angelo Harlan. AU - Lee, Albert. AU - Lu, Amelia Mac Kenzie. AU - Ross, Adam P.. AU - Borodinsky, Laura N.. AU - Marcucio, Ralph. AU - Trainor, Paul A.. AU - Zarbalis, Konstantinos. N1 - Funding Information: We thank Kirsten Lois Ner and Michael Podesta, for technical assistance. We also thank Dr. Athena Soulika for advice and support with flow cytometry. Funding. This study was supported by Shriners Hospitals for Children and NIH grant R01DE022830 to KZ, PT, and RM. Research in the Trainor laboratory is supported by the Stowers Institute for Medical Research.. PY - 2020/9/1. Y1 - 2020/9/1. N2 - Neural crest cells (NCCs) comprise a transient progenitor cell population of neuroepithelial origin that contributes to a variety of cell types throughout vertebrate embryos including most mesenchymal cells of the cranial and ...
Wounds within the oral mucosa, similarly to fetal wounds, exhibit rapid healing with reduced scarring. We hypothesized that a progenitor population resident within the oral mucosal lamina propria (OMLP) contributes to this preferential healing. Progenitor cells (PC) were reliably isolated from the OMLP by differential adhesion to fibronectin. Isolated colonies originating from a single cell demonstrated a rapid initial phase of proliferation, completing in excess of 50 population doublings (PDs) before entering cellular senescence. These data were supported by the expression of active telomerase within both developing colonies and expanded clones as assessed by immunocytochemistry (ICC) and the quantitative telomeric repeat amplification protocol. FACS analysis confirmed expression of the stem cell markers CD44, CD90, CD105, and CD166, but negative expression of CD34 and CD45 ruling out a hematopoietic or fibrocyte origin for these progenitors. A neural crest origin was confirmed by increased ...
Here we present the cloning of a full-length zebrafish pdgfr-α cDNA as well as the expression of this gene during zebrafish embryogenesis. We show that zebrafish pdgfr-α mRNA is present at high levels in the fertilized egg as well as in all embryonic cells up to the end of gastrulation. Spatially restricted expression of the gene started after the onset of segmentation and is mainly localized in premigratory neural crest cells, the placodes, the anterior paraxial cells of somites and the adaxial cells of the tailbud. Transient expression of this gene was also detected in the early Kupffers vesicle, a teleost-specific structure. Expression of the zebrafish pdgfr-α is both conserved as well as diverged comparing to that of other vertebrate species. © 2002 Elsevier Science Ireland Ltd. All rights reserved ...
Coreceptor for SEMA3A and SEMA3F. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance in the developing nervous system. Regulates the migration of sympathetic neurons, but not of neural crest precursors. Required for normal dendrite spine morphology in pyramidal neurons. May play a role in regulating semaphorin-mediated programmed cell death in the developing nervous system. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.
The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited despite the relevance for various fields of science and application. A series of genome-wide association studies on 78 facial shape phenotypes quantified from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci reaching genome-wide significant association, among which 17 were previously unreported. A multi-ethnic study in additional 7,917 individuals confirmed 13 loci including 8 unreported ones. A global map of polygenic face scores assembled facial features in major continental groups consistent with anthropological knowledge. Analyses of epigenomic datasets from cranial neural crest cells revealed abundant cis-regulatory activities at the face-associated genetic loci. Luciferase reporter assays in neural crest progenitor cells highlighted enhancer activities of several face-associated DNA variants. These results substantially advance our ...
Therefore, for my independent project, I have chosen to study the effects of substances that influence the brain like nicotine (cigarette smoke), n-Hexane, melatonin, and mercury on neurogenesis in fruit fly larvae. Regarding the cigarette smoke, I would like to pursue an experiment in which I compare the effects of electronic cigarette smoke to traditional cigarette smoke and see how they each affect neurogenesis. Neurogenesis is the growth and development of nervous tissues. Through larval brain and disc dissection, I will be able to get access to the larval brain and see how the drugs impacted the brain. I will use phosphohistone H3 (pH3) staining to give myself a visual representation of the proliferation in the neural crest cells. The more positively stained cells that are in each sample, the more proliferation. Furthermore, I will apply separate environmental stressors, which are changes in circadian rhythms and temperature to my experiment. ...
Thymus organogenesis requires coordinated interactions of multiple cell types, including neural crest (NC) cells, to orchestrate the formation, separation, and subsequent migration of the developing thymus from the third pharyngeal pouch to the thoracic cavity. The molecular mechanisms driving these processes are unclear; however, NC-derived mesenchyme has been shown to play an important role. Here, we show that, in the absence of ephrin-B2 expression on thymic NC-derived mesenchyme, the thymus remains in the cervical area instead of migrating into the thoracic cavity. Analysis of individual NC-derived thymic mesenchymal cells shows that, in the absence of ephrin-B2, their motility is impaired as a result of defective EphB receptor signaling. This implies a NC-derived cell-specific role of EphB-ephrin-B2 interactions in the collective migration of the thymic rudiment during organogenesis.
Injury and neurodegenerative conditions of the spinal cord can lead to paralysis and loss of sensation. Cell therapeutic approaches can restore sensory innervation of the spinal cord following injury and protect spinal cord cells from degeneration. This thesis primarily focuses on the restoration of deaffarented sensory fibres following injury to the dorsal root and spinal cord. These injuries lead to the formation of a non-permissive glial scar that prevents sensory axons from reinnervating spinal cord targets. It takes advantage of a dorsal root injury model that closely mimics spinal root avulsion injuries occurring in humans. In the first part of the thesis, three different neural progenitor types from human or murine sources are tested for their regenerative properties following their transplantation to the site of dorsal root avulsion injury. In the second part, the ability of murine neural progenitors to protect spinal motor neurons from a neurodegenerative process is tested.. In the ...
Ligand for members of the frizzled family of seven transmembrane receptors (By similarity). Shares much functionality with wnt11b. Signals through a non-canonical Wnt pathway to activate Jun-N-terminal kinase (JNK) to regulate gastrulation movements. Acts in a non-cell-autonomous manner to control neural crest migration, probably acting as an extracellular signal from surrounding tissue, but is not required for neural crest induction. Acts redundantly with wnt11b during pronephros induction. Regulates cardiac morphogenesis through the activation of JNK, but is not required for cardiac differentiation. Essential for dorsal fin development; required for an epithelial to mesenchymal transformation event prior to migration of cells into the fin, and ultimately for maintenance of fin structure. Mediates dorsal fin development through a non-canonical pathway mediated by Ca(2+) (By similarity).
Another study in the special feature by Marianne Bronner-Fraser, the second Albert Billings Ruddock Professor of Biology, focuses on the gene regulatory network underlying neural crest formation in the lamprey, the most primitive living vertebrate. The neural crest is a group of embryonic cells that are pinched off during the formation of the neural tube--the precursor to the spinal cord--and then migrate throughout the developing body to form other nervous system structures. The study reveals order and linkages within the network at early stages, Bronner-Fraser says. Because the neural crest cell type represents a vertebrate innovation, our work in lampreys shows that this network is ancient and tightly conserved to the base of vertebrates, she says.. The fourth of the Caltech papers, by Paul W. Sternberg, the Thomas Hunt Morgan Professor of Biology at Caltech and an investigator with the Howard Hughes Medical Institute (HHMI), and his colleagues, looks at a postembryonic gene regulatory ...
Why the interest in such an obscure cell? There is not a lot of information in the literature.. I am a clinician with a special interest in melanoma and, as such, you are continually struck by the potential aggressive and lethal nature of invasive melanoma and its resistance to therapeutics. There are some striking differences in behaviour between melanoma and its non-melanoma skin cancer relatives. Obviously, the melanocyte as the cell of origin, rather than the keratinocyte, and inevitably the neural crest origin of the melanocyte.. The Satellite cell, its close relative the Schwann cell, the melanocyte and its malignant offspring the melanoma cell, all share this Neural crest cell origin.. During evolutionary development, aspects of the Neural crest began to appear in early chordate species and eventually reached full expression in vertebrates. Protochordates were thin transparent sessile filter-feeders sitting in burrows on the sea floor but with evolutionary development grew in size, became ...
Our laboratory focuses on deciphering gene regulatory networks that govern complex programmes during early vertebrate development. We use systems approaches in specific cell types isolated directly from developing embryos to analyse transcriptional, epigenomic and cis-regulatory landscapes to decode and probe developmental programmes at the population and single-cell level. One of the intriguing developmental populations studied in our lab is the vertebrate neural crest. Neural crest (NC) is a unique multipotent embryonic cell population that differentiates into a plethora of diverse cell types, giving rise to structures as different as neurons and glia of peripheral nervous system, bone, cartilage and connective tissue elements of craniofacial skeleton and bodys pigmentation. Defects in neural crest patterning are some of the most common causes of birth anomalies, accounting for up to one-third of all congenital disabilities. Due to the unique multipotency, developmental plasticity and vast ...
Akbareian SE, Nagy N, Steiger CE, Mably JD, Miller SA, Hotta R, Molnar D, Goldstein AM: Enteric neural crest-derived cells promote their migration by modifying their microenvironment through tenascin-C production., DEVELOPMENTAL BIOLOGY 382: (2) pp. 446-456 ...
Vertebrate pigment cells are derived from neural crest, a tissue that also forms most of the peripheral nervous system and a variety of ectomesenchymal cell types. Formation of pigment cells from multipotential neural crest cells involves a number of common developmental processes. Pigment cells must be specified; their migration, proliferation, and survival must be controlled and they must differentiate to the final pigment cell type. We previously reported a large set of embryonic mutations that affect pigment cell development from neural crest (R. N. Kelsh et al., 1996, Development 123, 369-389). Based on distinctions in pigment cell appearance between mutants, we proposed hypotheses as to the process of pigment cell development affected by each mutation. Here we describe the cloning and expression of an early zebrafish melanoblast marker, dopachrome tautomerase. We used this marker to test predictions about melanoblast number and pattern in mutant embryos, including embryos homozygous for ...
Somites are transient, segmentally organized structures. In the vertebrate embryo, the somites contribute to multiple tissues, including the axial skeleton, skeletal and smooth muscles, dorsal dermis, tendons, ligaments, cartilage and adipose tissue. The somites also determine the migration paths of trunk neural crest cells and spinal nerve axons.. As the primitive streak regresses and the neural folds begin to gather at the center of the embryo, the paraxial mesoderm separates into blocks of cells called somites. These structures are formed by budding off as epithelial spheres from the cranial end of the unsegmented paraxial mesoderm that lies on either side of the neural tube.. The total number of somites formed is species-specific (38-39 in humans, 50 in chickens, 65 in mice) and is used as an indicator of embryonic developmental stages. Once formed, the epithelial somite is patterned rapidly into distinct compartments that subsequently give rise to distinct cell lineages. In response to ...
Orbital cartilage encircles the eye giving strength and support to the neural retina. It is derived from cranial neural crest cells (NCCs), cells that can generate a number of cell types including neurons, glia, and melanocytes. Uniquely in the head, NCCs also make skeletal derivatives that form the majority of the craniofacial skeleton. Differentiation of NCCs into cartilage requires inductive interactions between NCCs and the local environment. The nature of these interactions is largely unknown. We hypothesise that formation of the eye socket requires interactions between the eye and the NCCs during early development. This is supported by evidence in animals and humans where lack of eyes (anophthalmia) or formation of small eyes (microphthalmia) result in craniofacial abnormalities. Orbital cartilage is found in the majority of vertebrates but the ability to induce it has been lost to mammals. A comparison of chick and mouse should help us determine which tissues and molecules are necessary for this
1. Ebrahimi M, Taghi-Abadi E, Baharvand H. Limbal stem cells in review. J Ophthalmic Vis Res. 2009;4:40-58 2. Bahn CF, Falls HF, Varley GA, Meyer RF, Edelhauser HF, Bourne WM. Classification of corneal endothelial disorders based on neural crest origin. Ophthalmology. 1984;91:558-63 3. Bonanno JA. Identity and regulation of ion transport mechanisms in the corneal endothelium. Prog Retin Eye Res. 2003;22:69-94 4. Bourne WM, McLaren JW. Clinical responses of the corneal endothelium. Exp Eye Res. 2004;78:561-72 5. Lee JG, Kay EP. FGF-2-mediated signal transduction during endothelial mesenchymal transformation in corneal endothelial cells. Exp Eye Res. 2006;83:1309-16 6. Zhu YT, Chen HC, Chen SY, Tseng SC. Nuclear p120 catenin unlocks mitotic block of contact-inhibited human corneal endothelial monolayers without disrupting adherent junctions. J Cell Sci. 2012;125:3636-48 7. Chen HC, Zhu YT, Chen SY, Tseng SC. Wnt signaling induces epithelial-mesenchymal transition with proliferation in ARPE-19 ...
ENCODES a protein that exhibits bHLH transcription factor binding (ortholog); DNA-binding transcription factor activity, RNA polymerase II-specific (ortholog); DNA-binding transcription repressor activity, RNA polymerase II-specific (ortholog); INVOLVED IN angiogenesis (ortholog); blastocyst development (ortholog); cardiac left ventricle formation (ortholog); ASSOCIATED WITH Cardiomegaly (ortholog); Hereditary Neoplastic Syndromes (ortholog); hypoplastic left heart syndrome (ortholog); FOUND IN cytoplasm (ortholog); nuclear chromatin (ortholog); nucleolus (ortholog)
Biotagging, a genetically encoded toolkit in the zebrafish, reveals novel non-coding RNA players during neural crest and myocardium development ...
Read The fate of the neural crest in the head of the urodeles, The Journal of Comparative Neurology on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
Most textbooks say that Rathkes pouch invaginates from the oral ectoderm. Our observations and experiments give a different explanation for the chick embryo. We find that the roof, tip and floor of the pouch lie flat along the midline (A above), then the cephalic flexure through the mesencephalon as well as the downward bulging of the prosencephalon wrap the floor and roof around the tip of the pouch. We find that mesenchyme, mostly from mesencephalic neural crest, collects beneath the ectoderm lateral to the floor plate (and to some extent lateral to the roof plate) causing the walls of the pouch to form when the ectoderm lateral to the floor plate fuses with ectoderm lateral to roof plate ...
Diseases affecting heart function exact an enormous toll on human health, but many of the genetic and molecular mechanisms underlying heart disease remain unknown. Yost and colleagues discovered novel roles for the same developmental signaling pathway in two seemingly unrelated sources of cardiac dysfunction: adult heart failure and embryonic heart malformation. In their first study, the team found that a unique population of heart muscle cells derived from the embryonic neural crest is necessary for healthy heart function. These cells produce a ligand for the Notch signaling receptor, Jag2b, and the absence of the cell population or the jag2b gene during development results in heart failure in adult fish.. In a second study, they found that in a zebrafish model for Kabuki Syndrome, a congenital heart developmental disorder, Notch signaling is overactive. In a result with exciting implications for human patients, they showed that pharmacological inhibition of Notch signaling could restore normal ...
Chromaffin cells are neuroendocrine cells found predominantly in the medulla of the adrenal gland. They are also found in other ganglia of the sympathetic nervous system and are derived from the embryonic neural crest. Embryology They arise in ...
Video articles in JoVE about vitelline membrane include Application of Impermeable Barriers Combined with Candidate Factor Soaked Beads to Study Inductive Signals in the Chick, Dissection and Downstream Analysis of Zebra Finch Embryos at Early Stages of Development, A Submerged Filter Paper Sandwich for Long-term Ex Ovo Time-lapse Imaging of Early Chick Embryos, Using Fluorescence In Situ Hybridization (FISH) to Monitor the State of Arm Cohesion in Prometaphase and Metaphase I Drosophila Oocytes, Stem cell-like Xenopus Embryonic Explants to Study Early Neural Developmental Features In Vitro and In Vivo, In-vivo Centrifugation of Drosophila Embryos, Microinjection Wound Assay and In vivo Localization of Epidermal Wound Response Reporters in Drosophila Embryos., Blastomere Explants to Test for Cell Fate Commitment During Embryonic Development, Analysis of Neural Crest Migration and Differentiation by Cross-species Transplantation, Dual Labeling of Neural Crest Cells and Blood Vessels
This study briefly reviews the main events and processes that lead to the formation of the nervous system in mammals. At the end of gastrulation, they begin a series of fundamental morphogenetic processes with the formation of the neural plate (start of neurulation) culminating in the attainment of a normal nervous system. Embryological ectodermal primordia involved in the formation of the nervous system are the neuroectoblast, the neural crest cells and placodes that will evolve based on inductive phenomena, mainly from the notochord, prechordal plate and ectoderm. During the embryonic period consolidates the final development plan of the nervous system: 1) it comes complete neural tube formation when closing the rostral and caudal neuropores, 2) the different placodes invaginate to help form the organs of senses and sensory ganglia of the head, 3) the neural crest cells migrate to give rise to sensory and autonomic constituents of the peripheral nervous system and 4) developing brain vesicles, ...
Abzhanov A, Cordero DR, Sen J, Tabin CJ, Helms JAet al., 2007, Cross-regulatory interactions between Fgf8 and Shh in the avian frontonasal prominence., Congenit Anom (Kyoto), Vol: 47, Pages: 136-148, ISSN: 0914-3505 The frontonasal prominence of the developing avian embryo contains an organizing center, defined by juxtaposition of the Sonic hedgehog (Shh) and Fibroblast growth factor 8 (Fgf8) expression domains. This molecular interface presages any detectable growth of the frontonasal prominence, and experiments involving transplantation of this boundary epithelium have demonstrated it is a source of dorsal-ventral and rostral-caudal patterning information for the neural crest-derived mesenchyme of the upper beak. We explored the ontogeny of this organizing center by mapping the expression domains of both genes and their receptors and downstream targets. We tested the extent to which Shh and Fgf8 regulate each others expression in this frontonasal organizer by either blocking or ectopically ...
The origin of GnRH-1 neurons and OECs has been a matter of debate for several decades. Both cell types are associated with the olfactory/nasal placode (Schwanzel-Fukuda and Pfaff, 1989; Wray et al., 1989; Wewetzer et al., 2002; Barnett, 2004; Murdoch et al., 2010). During early development, the nasal placode and cranial neural crest cells share a common border, originating from ectoderm near the neural plate. Mixing of NC and olfactory placode cells has been suggested (Couly and Le Douarin, 1985; Whitlock, 2004; Schlosser, 2010). Thus, we used both NC and ectodermal-specific Cre-lox fate tracing strategies to determine the origin of nasal placode derivates. Here we show that early multipotent cranial NC cells mingle with ectodermally derived cells in the developing nasal placode where they generate (1) unique cell types such as the OECs and (2) neurons with similar features to those of ectodermal origin (Nagoshi et al., 2008, 2009) including a population of GnRH-1-expressing neurons.. The ...
The new version includes: Astrocytes lineage ; Updates to Kidney, Pancreas, Bone and Cartilage (from somite & neural crest) lineages ; 19 new high-throughput experiments for: hair, tooth, early embryo, cornea, lens and astrocytes ; New data from Bodymap & RNAseq ; 40 new protocols, including 7 new categories of direct reprogramming protocols added ; ~60 new patient-derived iPSCs ; Family cell descriptions for BM-MSCs, Adipose-derived MSCs and UC-MSCs (tissue) and 50 new cell therapies, including 7 cards of marketed cell-based products. Additionally, The UCB-MSCs (blood) cell family was split into tissue and cord blood with full elaborate descriptions. ...