RNA-binding protein Musashi family: roles for CNS stem cells and a subpopulation of ependymal cells revealed by targeted disruption and antisense ablation.
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Homologues of the Musashi family of RNA-binding proteins are evolutionarily conserved across species. In mammals, two members of this family, Musashi1 (Msi1) and Musashi2 (Msi2), are strongly coexpressed in neural precursor cells, including CNS stem cells. To address the in vivo roles of msi in neural development, we generated mice with a targeted disruption of the gene encoding Msi1. Homozygous newborn mice frequently developed obstructive hydrocephalus with aberrant proliferation of ependymal cells in a restricted area surrounding the Sylvius aqueduct. These observations indicate a vital role for msi1 in the normal development of this subpopulation of ependymal cells, which has been speculated to be a source of postnatal CNS stem cells. On the other hand, histological examination and an in vitro neurosphere assay showed that neither the embryonic CNS development nor the self-renewal activity of CNS stem cells in embryonic forebrains appeared to be affected by the disruption of msi1, but the diversity of the cell types produced by the stem cells was moderately reduced by the msi1 deficiency. Therefore, we performed antisense ablation experiments to target both msi1 and msi2 in embryonic neural precursor cells. Administration of the antisense peptide-nucleotides, which were designed to specifically down-regulate msi2 expression, to msi1(-/-) CNS stem cell cultures drastically suppressed the formation of neurospheres in a dose-dependent manner. Antisense-treated msi1(-/-) CNS stem cells showed a reduced proliferative activity. These data suggest that msi1 and msi2 are cooperatively involved in the proliferation and maintenance of CNS stem cell populations. (+info)
Subependymal pseudocysts in the fetal brain: prenatal diagnosis of two cases and review of the literature.
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Subependymal pseudocysts are cerebral cysts found in 5% of all neonates. When they are isolated and typical, they result from persistence of the germinal matrix, have a good prognosis and regress spontaneously within a few months. However, associated anomalies are frequent and in such cases the prognosis is poor. They can be of infectious, vascular, metabolic or chromosomal origin. Subependymal pseudocysts have rarely been described in the antenatal period. We report the prenatal diagnosis of two cases of isolated pseudocysts at 32 and 23 weeks. Both ultrasonography and magnetic resonance imaging assisted in the diagnosis and there was normal postnatal outcome in both cases. (+info)
A pilot study of cell production by the ganglionic eminences of the developing mouse brain.
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Cell production in the medial and lateral ganglionic eminences in pre- and post-natal mouse brains was studied by recording the number, location and plane of cleavage of mitotic figures. The site of maximum cell production shifted progressively from the ependymal layer to an adjacent sub-ependymal proliferative compartment. In the latter, mitosis occurred without the nuclei participating in the migratory movement to the ventricular surface which is characteristic of the nuclei of the ependymal compartment. The sub-ependymal compartment persisted vestigially into post-natal life as the well known sub-ependymal layer. (+info)
To beat or not to beat: roles of cilia in development and disease.
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Cilia and flagella appeared very early in evolution to provide unicellular organisms with motility in water. Adaptation to non-aquatic life in plants resulted in the almost complete elimination of these organelles, except for gametic transport in some phylogenetic groups. In contrast, cilia and flagella were retained and employed for a wide variety of functions requiring fluid movement in complex multicellular animals. The functions of cilia in diverse processes such as left-right axis pattern formation, cerebrospinal fluid flow, sensory reception, mucociliary clearance and renal physiology indicate that cilia have been adapted as versatile tools for many biological processes. In this review, we discuss recent discoveries that have extended knowledge of the roles of cilia in normal development, and the pathological consequences caused by their dysfunction in mammals. We also consider evolutionary relationships between cilia from lower and higher eukaryotes, outline the ciliary components required for assembly and motility, and review the terminology of axonemal heavy chain dynein genes. (+info)
Elevated vascular cell adhesion molecule-1 in AIDS encephalitis induced by simian immunodeficiency virus.
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AIDS encephalitis is a common sequela to HIV-1 infection in humans and simian immunodeficiency virus (SIVmac) infection in macaques. Although lentiviral-infected macrophages comprise parenchymal inflammatory infiltrates in affected brain tissue, the mechanisms responsible for leukocyte trafficking to the central nervous system in AIDS are unknown. In this study, we investigated the expression of various endothelial-derived leukocyte adhesion proteins in SIVmac-induced AIDS encephalitis. Encephalitic brains from SIVmac-infected macaques, but not uninflamed brains from other SIVmac-infected animals, were found to express abundant vascular cell adhesion molecule-1 (VCAM-1) protein on the majority of arteriolar, venular, and capillary endothelial cells. Soluble VCAM-1 concentrations in cerebrospinal fluid (CSF) from encephalitic animals were increased approximately 20-fold above those from animals without AIDS encephalitis. Expression of other endothelial-related adhesion molecules, including E-selectin, P-selectin, and intercellular adhesion molecule-1 (ICAM-1), was not uniformly associated with AIDS encephalitis. Thus, the presence of VCAM-1 in both brain and CSF was uniformly associated with SIVmac-induced disease of the central nervous system, and this expression may, at least in part, influence monocyte and lymphocyte recruitment to the central nervous system during the development of AIDS encephalitis. Moreover, measurement of soluble VCAM-1 in CSF may assist in the clinical assessment of animals or people with AIDS. (+info)
Reorganization of the ependyma during axolotl spinal cord regeneration: changes in intermediate filament and fibronectin expression.
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Changes in intermediate filament content and extracellular matrix material showed that the injury response of ependymal cells in lesioned axolotl spinal cord involves an epithelial-to-mesenchymal transformation, and that fibrous astrocytes are excluded from the remodeling lesion site. Antibody localization was used to visualize cytokeratin-, vimentin-, and glial fibrillary acidic protein- (GFAP-) containing intermediate filaments, as well as the adhesive glycoprotein fibronectin. In normal axolotl spinal cord cytokeratins were found near the apical surface of the ependymal cells. Transmission electron microscopic examination suggested that these cytokeratins were in tonofilaments. Cytokeratin expression was lost and vimentin production was initiated in ependymal cells 2-3 weeks following spinal cord injury. There was a period of approximately 1-2 weeks when cytokeratins and vimentin were co-expressed in vivo. This co-expression was maintained in vitro by culture on a fibronectin-coated substratum. As the central canal reformed, vimentin expression was lost. Ependymal cells lacked GFAP intermediate filaments, but GFAP was present in fibrous astrocytes of the neuropil and white matter. Following injury, GFAP localization showed that fibrous astrocytes disappeared from the remodeling lesion site and reappeared only after the ependymal epithelium reformed and newly myelinated axons were found. Fibronectin expression closely followed the expression of vimentin during mesenchymal ependymal cell outgrowth. These results suggest that the ependymal cell outgrowth requires changes in cell shape followed by changes in production of extracellular matrix. (+info)
THE FINE STRUCTURE OF EPENDYMA IN THE BRAIN OF THE RAT.
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The ciliated ependyma of the rat brain consists of a sheet of epithelial cells, the luminal surface of which is reflected over ciliary shafts and numerous evaginations of irregular dimensions. The relatively straight lateral portions of the plasmalemma of contiguous cells are fused at discrete sites to form five-layered junctions or zonulae occludentes which obliterate the intercellular space. These fusions occur usually at some distance below the free surface either independently or in continuity with a second intercellular junction, the zonula adhaerens. The luminal junction is usually formed by a zonula adhaerens or, occasionally, by a zonula occludens. The finely granular and filamentous cytoplasm contains supranuclear dense bodies, some of which are probably lysosomes and dense whorls of perinuclear filaments which send fascicles toward the lateral plasmalemma. The apical regions of the cytoplasm contain the basal body complexes of neighboring cilia. These complexes include a striated basal foot and short, non-striated rootlets emanating from the wall of each basal body. The rootlets end in a zone of granules about the proximal region of the basal body, adjacent to which may lie a striated mass of variable shape. All components of the basal body complex of adjacent cilia are independent of each other. (+info)
Tissue-specific expression of two isoforms of chicken fibroblast growth factor receptor, bek and Cek3.
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Chicken bek and Cek3 are isoforms of the fibroblast growth factor receptor which consist of primary structures that are identical except for a variation within the last of three immunoglobulin-like repeats in the ligand-binding domain. Northern blot analysis using isoform-specific probes revealed that the bek mRNA is expressed exclusively in lung, whereas the Cek3 mRNA is expressed prominently in brain and weakly in lung. We further localized these transcripts in brain and lung by in situ hybridization histochemistry. In lung, the expression of the bek and Cek3 transcripts was distinguished in the smooth muscle of the parabronchus and in the arterial adventitia. On the other hand, in brain, the Cek3 transcript was detected in three areas: the corpus medullare of the metencephalon (cerebellum), the archiastriatum of the telencephalon, and the ependymal cells of the ventriculare of the mesencephalon. Two putative exons corresponding to isoform-specific sequences, respectively, were found to be closely located on the chicken genome. These results indicate that bek/Cek3 isoforms are derived from the same premessenger and that their expression is regulated in a tissue- or even area-specific manner. Moreover, another potential isoform produced by a new splice site within the Cek3-specific exon has been isolated. (+info)