A glial-neuronal signaling pathway revealed by mutations in a neurexin-related protein. (25/31686)

In the nervous system, glial cells greatly outnumber neurons but the full extent of their role in determining neural activity remains unknown. Here the axotactin (axo) gene of Drosophila was shown to encode a member of the neurexin protein superfamily secreted by glia and subsequently localized to axonal tracts. Null mutations of axo caused temperature-sensitive paralysis and a corresponding blockade of axonal conduction. Thus, the AXO protein appears to be a component of a glial-neuronal signaling mechanism that helps to determine the membrane electrical properties of target axons.  (+info)

Mitochondrial gene expression is regulated at the level of transcription during early embryogenesis of Xenopus laevis. (26/31686)

Mitochondrial transcription in the early Xenopus laevis embryo resumes several hours before active mtDNA replication, effectively decoupling mtDNA transcription and replication. This developmental feature makes Xenopus embryogenesis an appealing model system to investigate the regulation of mitochondrial transcription. Studies reported here refine our understanding of the timing, magnitude, and mechanism of this transcriptional induction event. Northern analyses of six mitochondrial mRNAs (normalized to mtDNA) reveal that transcript levels remain basal between fertilization and gastrulation and then undergo a coordinate induction, culminating in a 20-28-fold increase over egg levels by 48 h of development. Measurement of mitochondrial run-on transcription rates demonstrates a good correlation between transcription rates and transcript levels, showing that transcription itself is the primary determinant of transcript abundance. Experimental increases in mitochondrial ATP and energy charge also correlate with patterns of transcript levels and transcription rates, suggesting that developmental changes in the biochemical composition of the mitochondrial matrix could be regulating transcriptional activity. Consistent with this idea, transcriptional run-on rates in mitochondria of early embryos can be stimulated by the addition of tricarboxylic acid cycle intermediates to the run-on reaction. However, mitochondria of later stages do not show this response to the addition of metabolite. In combination, these data suggest that mitochondrial transcription is under metabolic regulation during early Xenopus embryogenesis.  (+info)

Developmental regulation of spliced leader RNA gene in Leishmania donovani amastigotes is mediated by specific polyadenylation. (27/31686)

Leishmania cycles between the insect vector and its mammalian host undergoing several important changes mediated by the stage-specific expression of a number of genes. Using a genomic differential screening approach, we isolated differentially expressed cosmid clones carrying several copies of the mini-exon gene. We report that the spliced leader (SL) RNA, essential for the maturation of all pre-mRNAs by trans-splicing, is developmentally regulated in Leishmania donovani amastigotes and that this regulation is rapidly induced upon parasite growth under acidic conditions. Stage-specific regulation of the SL RNA is associated with the expression of a larger approximately 170-nucleotide transcript that bears an additional 15-nucleotide sequence at its 3'-end and is polyadenylated in contrast to the mature SL RNA. The poly(A)+ SL RNA represents 12-16% of the total SL transcript synthesized in amastigotes and is 2.5-3-fold more stable than the poly(A)- transcript. The poly(A)+ SL transcript is synthesized specifically from one class of the genomic mini-exon copies. Polyadenylation of the SL RNA may control the levels of the SL mature transcript under amastigote growth and may represent an additional step in the gene regulation process during parasite differentiation.  (+info)

From head to toes: the multiple facets of Sox proteins. (28/31686)

Sox proteins belong to the HMG box superfamily of DNA-binding proteins and are found throughout the animal kingdom. They are involved in the regulation of such diverse developmental processes as germ layer formation, organ development and cell type specifi-cation. Hence, deletion or mutation of Sox proteins often results in developmental defects and congenital disease in humans. Sox proteins perform their function in a complex interplay with other transcription factors in a manner highly dependent on cell type and promoter context. They exhibit a remarkable crosstalk and functional redundancy among each other.  (+info)

Characterization of a novel mouse cDNA, ES18, involved in apoptotic cell death of T-cells. (29/31686)

Using the modified screening approach in combination with expressed sequence tags, we have identified several novel cDNAs from mouse embryonic stem (ES) cells, whose expression is tissue-restricted and/or developmentally regulated. One of the cDNAs, ES18, is preferentially expressed in lymph node and thymus, and contains noteworthy features of transcriptional regulator. The expression of ES18 transcript was selectively regulated during the apoptosis of T-cell thymoma S49.1 induced by several stimuli. Interestingly, the ES18 transcript was differently regulated in the mutually antagonistic process, between dexamethasone- and A23187-induced cell death of T-cells. Moreover, the message level of ES18 was selectively enhanced by staurosporine, a broad protein kinase inhibitor, but not by other protein kinase inhibitors such as GF109203X and H89. In addition, ES18 transcript was induced by C2-ceramide, which is a mediator of both dexamethasone- and staurosporine-induced apoptotic signaling. We further showed that transient overexpression of ES18 in mouse T-cell lymphoma increased the apoptotic cell death. These data suggest that ES18 may be selectively involved in specific apoptotic processes in mouse T-cells.  (+info)

The Dictyostelium developmental cDNA project: generation and analysis of expressed sequence tags from the first-finger stage of development. (30/31686)

In an effort to identify and characterize genes expressed during multicellular development ill Dictyostelium, we have undertaken a cDNA sequencing project. Using size-fractionated subsets of cDNA from the first finger stage, two sets of gridded libraries were constructed for cDNA sequencing. One, library S, consisting of 9984 clones, carries relatively short inserts, and the other, library L, which consists of 8448 clones, has longer inserts. We sequenced all the selected clones in library S from their 3'-ends, and this generated 3093 non-redundant, expressed sequence tags (ESTs). Among them, 246 ESTs hit known Dictyostelium genes and 910 showed significant similarity to genes of Dictyostelium and other organisms. For library L, 1132 clones were randomly sequenced and 471 non-redundant ESTs were obtained. In combination, the ESTs from the two libraries represent approximately 40% of genes expressed in late development, assuming that the non-redundant ESTs correspond to independent genes. They will provide a useful resource for investigating the genetic networks that regulate multicellular development of this organism.  (+info)

Bmp4 is required for the generation of primordial germ cells in the mouse embryo. (31/31686)

In many organisms the allocation of primordial germ cells (PGCs) is determined by the inheritance of maternal factors deposited in the egg. However, in mammals, inductive cell interactions are required around gastrulation to establish the germ line. Here, we show that Bmp4 homozygous null embryos contain no PGCs. They also lack an allantois, an extraembryonic mesodermal tissue derived, like the PGCs, from precursors in the proximal epiblast. Heterozygotes have fewer PGCs than normal, due to a reduction in the size of the founding population and not to an effect on its subsequent expansion. Analysis of beta-galactosidase activity in Bmp4(lacZneo) embryos reveals that prior to gastrulation, Bmp4 is expressed in the extraembryonic ectoderm. Later, Bmp4 is expressed in the extraembryonic mesoderm, but not in PGCs. Chimera analysis indicates that it is the Bmp4 expression in the extraembryonic ectoderm that regulates the formation of allantois and primordial germ cell precursors, and the size of the founding population of PGCs. The initiation of the germ line in the mouse therefore depends on a secreted signal from the previously segregated, extraembryonic, trophectoderm lineage.  (+info)

The Caenorhabditis elegans gene ham-2 links Hox patterning to migration of the HSN motor neuron. (32/31686)

The Caenorhabditis elegans HSN motor neurons permit genetic analysis of neuronal development at single-cell resolution. The egl-5 Hox gene, which patterns the posterior of the embryo, is required for both early (embryonic) and late (larval) development of the HSN. Here we show that ham-2 encodes a zinc finger protein that acts downstream of egl-5 to direct HSN cell migration, an early differentiation event. We also demonstrate that the EGL-43 zinc finger protein, also required for HSN migration, is expressed in the HSN specifically during its migration. In an egl-5 mutant background, the HSN still expresses EGL-43, but expression is no longer down-regulated at the end of the cell's migration. Finally, we find a new role in early HSN differentiation for UNC-86, a POU homeodomain transcription factor shown previously to act downstream of egl-5 in the regulation of late HSN differentiation. In an unc-86; ham-2 double mutant the HSNs are defective in EGL-43 down-regulation, an egl-5-like phenotype that is absent in either single mutant. Thus, in the HSN, a Hox gene, egl-5, regulates cell fate by activating the transcription of genes encoding the transcription factors HAM-2 and UNC-86 that in turn individually control some differentiation events and combinatorially affect others.  (+info)