Primordial germ cells: the first cell lineage or the last cells standing?

Abstract

Embryos of many animal models express germ line determinants that suppress transcription and mediate early germ line commitment, which occurs before the somatic cell lineages are established. However, not all animals segregate their germ line in this manner. The 'last cell standing' model describes primordial germ cell (PGC) development in axolotls, in which PGCs are maintained by an extracellular signalling niche, and germ line commitment occurs after gastrulation. Here, we propose that this 'stochastic' mode of PGC specification is conserved in vertebrates, including non-rodent mammals. We postulate that early germ line segregation liberates genetic regulatory networks for somatic development to evolve, and that it therefore emerged repeatedly in the animal kingdom in response to natural selection.

Keywords: Amphibian embryo; Evolvability; Germ plasm; Mammalian embryo; PGC; Pluripotency; Primordial germ cell.

Fig. 1.

Primordial germ cell specification in mice, axolotls and frogs. (A,B) In mice (A) and axolotls (B), BMP is a key inductive molecule required for the specification of germ cell precursors (Lawson et al., 1999; Chatfield et al., 2014). (C) In Xenopus, germ plasm components inherited from the egg are passed to a group of cells in the endoderm of the developing embryo that become PGCs (Blackler, 1962). DL, dorsal lip; Epi, epiblast; ExE, extra-embryonic ectoderm; Tr, trophectoderm; VE, visceral endoderm. Yellow circles depict primordial germ cell precursors. In the case of Xenopus, the red centre depicts the germ plasm.

Fig. 2.

Gene regulatory networks for early development have been modified in Xenopus. Pluripotency is established at the midblastula transition (MBT) in amphibians. Frogs have lost key components of the pluripotency network (specifically, Nanog and Oct4) that are conserved between urodele amphibians and mammals. Furthermore, the GRN that regulates mesoderm specification in Xenopus has expanded. By comparison with the GRN for mesoderm in axolotl, the Xenopus GRN shows novel features, including expansion of the Nodal (25 orthologues, denoted Xnr) and Mix (seven orthologues) gene families, Nodal gene expression prior to the midblastula stage, and altered topological relationships. See Swiers et al. (2010) for details.

Fig. 3.

Differences in early embryo morphology within mammals. (A-D) In mouse (A,B), the egg cylinder forms as a result of the cavitation of the embryo after the formation of the extra-embryonic ectoderm. In most other mammals, the epiblast does not undergo cavitation and forms a flat embryonic disc that is surrounded by extra-embryonic membranes (C,D). An image of a pig embryo (C) around the onset of gastrulation shows the configuration of a typical non-rodent mammalian embryonic disc surrounded by trophectoderm (or trophoblast). ED, embryonic disc; Epi, epiblast; ExE, extra-embryonic ectoderm; M, mesoderm; Tr, trophoblast; VE, visceral endoderm. The proximal (P)-distal (D) and anterior (A)-posterior (P) axes are indicated.

Fig. 4.

A model for PGC specification in non-rodent mammals. (A) Top and lateral views of the three germ layers of a peri-gastrulation embryo and the location of presumptive PGC precursors (red dots). (B) Detailed sagittal view of three developmental stages of an early to mid-gastrulation embryo. At the pre-streak stage, BMP2 produced in the posterior primitive endoderm contributes to the induction of the initial delamination of epiblast cells into the mesodermal layer. These cells expand and they start to produce BMP4 (early streak stage), contributing to the further expansion of the mesoderm. Later, at the mid-streak stage, a cluster of cells located in the midline of the embryo, posterior to the primitive streak, is induced by BMPs to initiate the germ cell programme. M, mesoderm. The anterior (A)-posterior (P) axes are indicated.

Fig. 5.

A correlation between early germ line commitment and enhanced speciation. All frogs studied contain germ plasm (Nieuwkoop and Sutasurya, 1979). All teleost embryos are likely to contain germ plasm (Herpin et al., 2007; Knaut et al., 2002). Also, all turtle species that have been studied use the inductive mode (Bachvarova et al., 2009a,b). The situation for other reptiles is more ambiguous. Among mammals, the rodent lineage accounts for ∼40% of all species. Numbers in brackets indicate the number of species.