Germ Cells: Sex and Repression in Mice

The mouse Blimp1 gene encodes a transcriptional repressor that is essential for B-cell development. Recent studies have shown that the Blimp1 protein also plays a critical role in the specification of mouse primordial germ cells

The function and regulation of vasa-like genes in germ-cell development

The vasa gene, essential for germ-cell development, was originally identified in Drosophila, and has since been found in other invertebrates and vertebrates. Analysis of these vasa homologs has revealed a highly conserved role for Vasa protein among different organisms, as well as some important differences in its regulation

Fluid dynamics during bleb formation in migrating cells in vivo

Blebs are cellular protrusions observed in migrating cells and in cells undergoing spreading, cytokinesis, and apoptosis. Here we investigate the flow of cytoplasm during bleb formation and the concurrent changes in cell volume using zebrafish primordial germ cells (PGCs) as an in vivo model. We show that bleb inflation occurs concomitantly with cytoplasmic inflow into it and that during this process the total cell volume does not change. We thus show that bleb formation in primordial germ cells results primarily from redistribution of material within the cell rather than being driven by flow of water from an external source

Specification of primordial germ cells in medaka (Oryzias latipes)

BACKGROUND: Primordial germ cells (PGCs) give rise to gametes that are responsible for the development of a new organism in the next generation. Two modes of germ line specification have been described: the inheritance of asymmetrically-localized maternally provided cytoplasmic determinants and the induction of the PGC fate by other cell types. PGCs specification in zebrafish appears to depend on inheritance of germ plasm in which several RNA molecules such as vasa and nanos reside. Whether the specification mode of PGCs found in zebrafish is general for other fish species was brought into question upon analysis of olvas expression – the vasa homologue in another teleost, medaka (Oryzias latipes). Here, in contrast to the findings in zebrafish, the PGCs are found in a predictable position relative to a somatic structure, the embryonic shield. This finding, coupled with the fact that vasa mRNA, which is localized to the germ plasm of zebrafish but does not label a similar structure in medaka opened the possibility of fundamentally different mechanisms governing PGC specification in these two fish species. RESULTS: In this study we addressed the question concerning the mode of PGC specification in medaka using embryological experiments, analysis of RNA stability in the PGCs and electron microscopy observations. Dramatic alterations in the somatic environment, i.e. induction of a secondary axis or mesoderm formation alteration, did not affect the PGC number. Furthermore, the PGCs of medaka are capable of protecting specific RNA molecules from degradation and could therefore exhibit a specific mRNA expression pattern controlled by posttrancriptional mechanisms. Subsequent analysis of 4-cell stage medaka embryos using electron microscopy revealed germ plasm-like structures located at a region corresponding to that of zebrafish germ plasm. CONCLUSION: Taken together, these results are consistent with the idea that in medaka the inheritance of maternally provided asymmetrically-localized cytoplasmic determinants directs cells to assume the germ line fate similar to zebrafish PGCs

Zebrafish Primordial Germ Cell Migration

Similar to many other organisms, zebrafish primordial germ cells (PGCs) are specified at a location distinct from that of gonadal somatic cells. Guided by chemotactic cues, PGCs migrate through embryonic tissues toward the region where the gonad develops. In this process, PGCs employ a bleb-driven amoeboid migration mode, characterized by low adhesion and high actomyosin contractility, a strategy used by other migrating cells, such as leukocytes and certain types of cancer cells. The mechanisms underlying the motility and the directed migration of PGCs should be robust to ensure arrival at the target, thereby contributing to the fertility of the organism. These features make PGCs an excellent model for studying guided single-cell migration in vivo. In this review, we present recent findings regarding the establishment and maintenance of cell polarity that are essential for motility and discuss the mechanisms by which cell polarization and directed migration are controlled by chemical and physical cues

Sequential SDF1a and b-induced mobility guides Medaka PGC migration

AbstractAssembly and formation of the gonad primordium are the first steps toward gonad differentiation and subsequent sex differentiation. Primordial germ cells (PGCs) give rise to the gametes that are responsible for the development of a new organism in the next generation. In many organisms, following their specification the germ cells migrate toward the location of the prospective gonadal primordium. To accomplish this, the PGCs obtain directional cues from cells positioned along their migration path. One such cue, the chemokine SDF1 (stromal cell-derived factor 1) and its receptor CXCR4 have recently been found to be critical for proper PGC migration in zebrafish, chick and mouse.We have studied the mechanisms responsible for PGC migration in Medaka. In contrast to the situation observed in zebrafish, where proper PGC positioning is the result of active migration in the direction of the source of SDF1a, Medaka PGC movements are shown to be the consequence of a combination of active SDF1a and SDF1b-guided migration. In this process both SDF1 co-orthologues show only partly overlapping expression pattern and cooperate in the correct positioning of the PGCs

CXCR7 Functions as a Scavenger for CXCL12 and CXCL11

CXCR7 (RDC1), the recently discovered second receptor for CXCL12, is phylogenetically closely related to chemokine receptors, but fails to couple to G-proteins and to induce typical chemokine receptor mediated cellular responses. The function of CXCR7 is controversial. Some studies suggest a signaling activity in mammalian cells and zebrafish embryos, while others indicate a decoy activity in fish. Here we investigated the two propositions in human tissues. We provide evidence and mechanistic insight that CXCR7 acts as specific scavenger for CXCL12 and CXCL11 mediating effective ligand internalization and targeting of the chemokine cargo for degradation. Consistently, CXCR7 continuously cycles between the plasma membrane and intracellular compartments in the absence and presence of ligand, both in mammalian cells and in zebrafish. In accordance with the proposed activity as a scavenger receptor CXCR7-dependent chemokine degradation does not become saturated with increasing ligand concentrations. Active CXCL12 sequestration by CXCR7 is demonstrated in adult mouse heart valves and human umbilical vein endothelium. The finding that CXCR7 specifically scavenges CXCL12 suggests a critical function of the receptor in modulating the activity of the ubiquitously expressed CXCR4 in development and tumor formation. Scavenger activity of CXCR7 might also be important for the fine tuning of the mobility of hematopoietic cells in the bone marrow and lymphoid organs