Primordial germ cell migration in the chick and mouse embryo: the role of the chemokine SDF-1/CXCL12.

As in many other animals, the primordial germ cells (PGCs) in avian and reptile embryos are specified in positions distinct from the positions where they differentiate into sperm and egg. Unlike in other organism however, in these embryos, the PGCs use the vascular system as a vehicle to transport them to the region of the gonad where they exit the blood vessels and reach their target. To determine the molecular mechanisms governing PGC migration in these species, we have investigated the role of the chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) in guiding the cells towards their target in the chick embryo. We show that sdf-1 mRNA is expressed in locations where PGCs are found and towards which they migrate at the time they leave the blood vessels. Ectopically expressed chicken SDF-1alpha led to accumulation of PGCs at those positions. This analysis, as well as analysis of gene expression and PGC behavior in the mouse embryo, suggest that in both organisms, SDF-1 functions during the second phase of PGC migration, and not at earlier phases. These findings suggest that SDF-1 is required for the PGCs to execute the final migration steps as they transmigrate through the blood vessel endothelium of the chick or the gut epithelium of the mouse.

Transcriptional profiling identifies genes differentially expressed during and after migration in murine primordial germ cells.

Mouse primordial germ cells (PGCs) are migratory until they colonize the genital ridges, assemble with the somatic tissue, and start to differentiate into oocytes or spermatogonia. Using cell transplantation experiments, we show here that germ cells isolated during migration (at E10.5) will migrate actively to the genital ridges, whereas post-migratory PGCs isolated from E12.5 embryos are non-motile even when transferred into a permissive environment (e.g. E10.5 host tissue). Major transcriptional changes must take place between E10.5 and E12.5 that convert germ cells from a migratory to a non-migratory state. To identify the genes involved, we have performed transcriptional profiling of motile and non-motile populations of PGCs. We have identified 55 transcripts that are expressed in E10.5 PGCs at levels at least 3 x their expression at E12.5, and 48 transcripts with the reciprocal expression levels. Additionally, 309 transcripts were found to be expressed in both populations. Many of the E10.5 transcripts encode proteins involved in controlling cytoskeletal and adhesive interactions implicated in cell motility. Many of the E12.5 transcripts encode proteins implicated in germ cell differentiation.

GP130, the shared receptor for the LIF/IL6 cytokine family in the mouse, is not required for early germ cell differentiation, but is required cell-autonomously in oocytes for ovulation.

GP130 is the shared receptor for members of the IL6 family of cytokines. Members of this family have been shown to enhance the survival of migratory (E10.5) or postmigratory (E12.5) murine primordial germ cells (PGCs) in culture; however, it is uncertain what role these cytokines play during PGC development in vivo. We have examined PGC numbers in E13.5 GP130-deficient mouse embryos and found that males exhibited a slight decrease in PGC numbers; females were normal. Also, we used the Cre-loxP system to inactive GP130 specifically in germ cells and found that this resulted in a fertility defect in females. These animals were found to have a slight reduction in the number of primary follicles and a major defect in ovulation. This data suggests that GP130 is required in female germ cells for their normal function, but is dispensable in male germ cells.