Biomedical subjects

Girish Deshpande

Publications and source records attributed to Girish Deshpande.

7 recordsLinked to original sources

PubMed2006

The drosophila fragile X protein dFMR1 is required during early embryogenesis for pole cell formation and rapid nuclear division cycles.

The FMR family of KH domain RNA-binding proteins is conserved from invertebrates to humans. In humans, inactivation of the X-linked FMR gene fragile X is the most common cause of mental retardation and leads to defects in neuronal architecture. While there are three FMR family members in humans, there is only a single gene, dfmr1, in flies. As in humans, inactivation of dfmr1 causes defects in neuronal architecture and in behavior. dfmr1 has other functions in the fly in addition to neurogenesis. Here we have analyzed its role during early embryonic development. We found that dfmr1 embryos display defects in the rapid nuclear division cycles that precede gastrulation in nuclear migration and in pole cell formation. While the aberrations in nuclear division are correlated with a defect in the assembly of centromeric/centric heterochromatin, the defects in pole cell formation are associated with alterations in the actin-myosin cytoskeleton.

Animals↗

PubMed2005

Drosophila argonaute-2 is required early in embryogenesis for the assembly of centric/centromeric heterochromatin, nuclear division, nuclear migration, and germ-cell formation.

The RNA-induced silencing complex (RISC) or the RISC complex mediates RNAi and is comprised of proteins belonging to the dicer and Argonaute family proteins. Here we show that Argonaute-2 (ago-2) is required for proper nuclear migration, pole cell formation, and cellularization during the early stages of embryonic development in Drosophila. We have traced these defects back to the nuclear division cycles. Unlike wild type, nuclear division is asynchronous in ago-2 embryos and there are defects in chromosome condensation, nuclear kinesis, and assembly of spindle apparatus. The aberrations in the nuclear division cycle are correlated with defects in the formation of centric/centromeric heterochromatin and point to a failure in the assembly of functional centromeres.

Actins↗

PubMed2005

Nanos downregulates transcription and modulates CTD phosphorylation in the soma of early Drosophila embryos.

nanos (nos) specifies posterior development in the Drosophila embryo by repressing the translation of maternal hb mRNA. In addition to this somatic function, nos is required in the germline progenitors, the pole cells, to establish transcriptional quiescence. We have previously reported that nos is required to keep the Sex-lethal establishment promoter, Sxl-Pe, off in the germline of both sexes. We show here that nos also functions to repress Sxl-Pe activity in the surrounding soma. Sxl-Pe is inappropriately activated in the soma of male embryos from nos mothers, while Sxl-Pe can be repressed in female embryos by ectopic Nos protein. nos appears to play a global role in repressing transcription in the soma as the effects of nos on promoter activity are correlated with changes in the phosphorylation status of the carboxy terminal domain (CTD) repeats of the large RNA polymerase II subunit. Finally, we present evidence indicating that the suppression of transcription in the soma by Nos protein is important for normal embryonic development.

3' Untranslated Regions↗

PubMed2005

HMGCoA reductase potentiates hedgehog signaling in Drosophila melanogaster.

Drosophila HMGCoA reductase (hmgcr) catalyzes the biosynthesis of a mevalonate precursor for isoprenoids and has been implicated in the production of a signal by the somatic gonadal precursor cells (SGPs) that attracts migrating germ cells. Here, we show that hmgcr functions in the hedgehog (hh) signaling pathway. When hmgcr activity is reduced, high levels of Hh accumulate in hh-expressing cells in each parasegment, while the adjacent "Hh-receiving" cells cannot sustain wg expression and fail to relocalize the Smoothened (Smo) receptor. Conversely, ectopic Hmgcr upregulates Hh signaling when it is produced in hh-expressing cells, but has no effect when produced in the receiving cells. These findings suggest that Hmgcr might orchestrate germ cell migration by promoting the release and/or transport of Hh from the SGPs. Consistent with this model, there are substantial germ cell migration defects in trans combinations between hmgcr and mutations in different components of the hh pathway.

Animals↗

PubMed2004

Overlapping mechanisms function to establish transcriptional quiescence in the embryonic Drosophila germline.

In Drosophila melanogaster, the germline precursor cells, i.e. pole cells, are formed at the posterior of the embryo. As observed for newly formed germ cells in many other eukaryotes, the pole cells are distinguished from the soma by their transcriptional quiescence. To learn more about the mechanisms involved in establishing quiescence, we ectopically expressed a potent transcriptional activator, Bicoid (Bcd), in pole cells. We find that Bcd overrides the machinery that downregulates transcription, and activates not only its target gene hunchback but also the normally female specific Sex-lethal promoter, Sxl-Pe, in the pole cells of both sexes. Unexpectedly, the terminal pathway gene torso-like is required for Bcd-dependent transcription. However, terminal signaling is known to be attenuated in pole cells, and this raises the question of how this is accomplished. We present evidence indicating that polar granule component (pgc) is required to downregulate terminal signaling in early pole cells. Consistently, pole cells compromised for pgc function exhibit elevated levels of activated MAP kinase and premature transcription of the target gene tailless (tll). Furthermore, pgc is required to establish a repressive chromatin architecture in pole cells.

3' Untranslated Regions↗

PubMed2003

A conserved chromatin architecture marks and maintains the restricted germ cell lineage in worms and flies.

In C. elegans, mRNA production is initially repressed in the embryonic germline by a protein unique to C. elegans germ cells, PIE-1. PIE-1 is degraded upon the birth of the germ cell precursors, Z2 and Z3. We have identified a chromatin-based mechanism that succeeds PIE-1 repression in these cells. A subset of nucleosomal histone modifications, methylated lysine 4 on histone H3 (H3meK4) and acetylated lysine 8 on histone H4 (H4acetylK8), are globally lost and the DNA appears more condensed. This coincides with PIE-1 degradation and requires that germline identity is not disrupted. Drosophila pole cell chromatin also lacks H3meK4, indicating that a unique chromatin architecture is a conserved feature of embryonic germ cells. Regulation of the germline-specific chromatin architecture requires functional nanos activity in both organisms. These results indicate that genome-wide repression via a nanos-regulated, germ cell-specific chromatin organization is a conserved feature of germline maintenance during embryogenesis.

Animals↗

PubMed2002

First seduction, then transfiguration.

Members of the fibroblast growth factor (FGF) family contribute to various cellular processes. Recent reports elucidate the involvement of FGFs as chemoattractants that influence diverse cellular events such as imaginal patterning in Drosophila and gastrulation in amniotes. These studies underscore the enticing activity of FGFs and raise interesting questions regarding subsequent transformations in cellular identity.

Animals↗