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Prabhat S Kunwar

Publications and source records attributed to Prabhat S Kunwar.

6 recordsLinked to original sources
PubMed2006

In vivo migration: a germ cell perspective.

The basic concepts of the molecular machinery that mediates cell migration have been gleaned from cell culture systems. However, the three-dimensional environment within an organism presents migrating cells with a much greater challenge. They must move between and among other cells while interpreting multiple attractive and repulsive cues to choose their proper path. They must coordinate their cell adhesion with their surroundings and know when to start and stop moving. New insights into the control of these remaining mysteries have emerged from genetic dissection and live imaging of germ cell migration in Drosophila, zebrafish, and mouse embryos. In this review, we first describe germ cell migration in cellular and mechanistic detail in these different model systems. We then compare these systems to highlight the emerging principles. Finally, we contrast the migration of germ cells with that of immune and cancer cells to outline the conserved and different mechanisms.

Animals↗
PubMed2004

A noncoding RNA is required for the repression of RNApolII-dependent transcription in primordial germ cells.

RNApolII-dependent transcription is repressed in primordial germ cells of many animals during early development and is thought to be important for maintenance of germline fate by preventing somatic differentiation. Germ cell transcriptional repression occurs concurrently with inhibition of phosphorylation in the carboxy-terminal domain (CTD) of RNApolII, as well as with chromatin remodeling. The precise mechanisms involved are unknown. Here, we present evidence that a noncoding RNA transcribed by the gene polar granule component (pgc) regulates transcriptional repression in Drosophila germ cells. Germ cells lacking pgc RNA express genes important for differentiation of nearby somatic cells and show premature phosphorylation of RNApolII. We further show that germ cells lacking pgc show increased levels of K4, but not K9 histone H3 methylation, and that the chromatin remodeling Swi/Snf complex is required for a second stage in germ cell transcriptional repression. We propose that a noncoding RNA controls transcription in early germ cells by blocking the transition from preinitiation to transcriptional elongation. We further show that repression of somatic differentiation signals mediated by the Torso receptor-tyrosine kinase is important for germline development.

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PubMed2003

Tre1, a G protein-coupled receptor, directs transepithelial migration of Drosophila germ cells.

In most organisms, germ cells are formed distant from the somatic part of the gonad and thus have to migrate along and through a variety of tissues to reach the gonad. Transepithelial migration through the posterior midgut (PMG) is the first active step during Drosophila germ cell migration. Here we report the identification of a novel G protein-coupled receptor (GPCR), Tre1, that is essential for this migration step. Maternal tre1 RNA is localized to germ cells, and tre1 is required cell autonomously in germ cells. In tre1 mutant embryos, most germ cells do not exit the PMG. The few germ cells that do leave the midgut early migrate normally to the gonad, suggesting that this gene is specifically required for transepithelial migration and that mutant germ cells are still able to recognize other guidance cues. Additionally, inhibiting small Rho GTPases in germ cells affects transepithelial migration, suggesting that Tre1 signals through Rho1. We propose that Tre1 acts in a manner similar to chemokine receptors required during transepithelial migration of leukocytes, implying an evolutionarily conserved mechanism of transepithelial migration. Recently, the chemokine receptor CXCR4 was shown to direct migration in vertebrate germ cells. Thus, germ cells may more generally use GPCR signaling to navigate the embryo toward their target.

Animals↗
PubMed2003

Mixer/Bon and FoxH1/Sur have overlapping and divergent roles in Nodal signaling and mesendoderm induction.

Transcription factors belonging to the FoxH1 and Mixer families are required for facets of Nodal signaling during vertebrate mesendoderm induction. Here, we analyze whether zebrafish proteins related to FoxH1 [Schmalspur (Sur)] and Mixer [Bonnie and clyde (Bon)] act within or downstream of the Nodal signaling pathway, test whether these two factors have additive or overlapping activities, and determine whether FoxH1/Sur and Mixer/Bon can account for all Nodal signaling during embryogenesis. We find that sur expression is independent of Nodal signaling and that bon is expressed in the absence of Nodal signaling but requires Nodal signaling and Sur for enhanced, maintained expression. These results and the association of FoxH1 and Mixer/Bon with phosphorylated Smad2 support a role for these factors as components of the Nodal signaling pathway. In contrast to the relatively mild defects observed in single mutants, loss of both bon and sur results in a severe phenotype characterized by absence of prechordal plate, cardiac mesoderm, endoderm and ventral neuroectoderm. Analysis of Nodal-regulated proteins reveals that Bon and Sur have both distinct and overlapping regulatory roles. Some genes are regulated by both Bon and Sur, and others by either Bon or Sur. Complete loss of Nodal signaling results in a more severe phenotype than loss of both Bon and Sur, indicating that additional Smad-associated transcription factors remain to be identified that act as components of the Nodal signaling pathway.

Animals↗
PubMed2003

The chemokine SDF1/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival.

In mouse embryos, germ cells arise during gastrulation and migrate to the early gonad. First, they emerge from the primitive streak into the region of the endoderm that forms the hindgut. Later in development, a second phase of migration takes place in which they migrate out of the gut to the genital ridges. There, they co-assemble with somatic cells to form the gonad. In vitro studies in the mouse, and genetic studies in other organisms, suggest that at least part of this process is in response to secreted signals from other tissues. Recent genetic evidence in zebrafish has shown that the interaction between stromal cell-derived factor 1 (SDF1) and its G-protein-coupled receptor CXCR4, already known to control many types of normal and pathological cell migrations, is also required for the normal migration of primordial germ cells. We show that in the mouse, germ cell migration and survival requires the SDF1/CXCR4 interaction. First, migrating germ cells express CXCR4, whilst the body wall mesenchyme and genital ridges express the ligand SDF1. Second, the addition of exogenous SDF1 to living embryo cultures causes aberrant germ cell migration from the gut. Third, germ cells in embryos carrying targeted mutations in CXCR4 do not colonize the gonad normally. However, at earlier stages in the hindgut, germ cells are unaffected in CXCR4(-/-) embryos. Germ cell counts at different stages suggest that SDF1/CXCR4 interaction also mediates germ cell survival. These results show that the SDF1/CXCR4 interaction is specifically required for the colonization of the gonads by primordial germ cells, but not for earlier stages in germ cell migration. This demonstrates a high degree of evolutionary conservation of part of the mechanism, but also an area of evolutionary divergence.

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