Physiologic Course of Female Reproductive Function: A Molecular Look into the Prologue of Life

Figure 4

Factors controlling specification and migration of primordial germ cells. bFGF: basic fibroblast growth factor; FGF: fibroblast growth factor; PGC: primordial germ cells; SCF: Stem Cell Factor; SDF1: stromal cell-derived factor. Formation of fully competent gonads demands the presence of PGC in the genital primordia, which in turn requires the fulfillment of two fundamental processes. (1) Specification: PGC stem from a small group of cells which are subjected to induction by the extraembryonic ectoderm, via intense BMP4 signaling, which induces expression of BLIMP1 in these cells. The main factors controlling specification are the expression of pluripotent genes, for example, Oct4, Sox2, and Nanog, and thorough epigenetic reprogramming. In addition, BLIMP1 and LIN28 allow expression of DPPA3 (Stella), which mediates protection of maternal imprinting in PGC. (2) Migration: PGC initially reside with the epiblast in the gastrula in the posterior end of the primitive streak, which will later become the extraembryonic mesoderm. Then, PGC migrate through the allantois and reside temporarily in the yolk sac. These cells then migrate caudally through the hindgut towards the dorsal mesentery and then the urogenital ridges, their definitive location. The principal factors regulating this process are SDF1 and SCF, which bind to CXCR4 and c-KIT, respectively, mediating chemotaxis and survival of PGC.