BMP signals and the transcriptional repressor BLIMP1 during germline segregation in the mammalian embryo

Abstract

Molecular factors and tissue compartments involved in the foundation of the mammalian germline have been mainly described in the mouse so far. To find mechanisms applicable to mammals in general, we analyzed temporal and spatial expression patterns of the transcriptional repressor BLIMP1 (also known as PRDM1) and the signaling molecules BMP2 and BMP4 in perigastrulation and early neurulation embryos of the rabbit using whole-mount in situ hybridization and high-resolution light microscopy. Both BMP2 and BMP4 are expressed in annular domains at the boundary of the embryonic disc, which—in contrast to the situation in the mouse—partly belong to intraembryonic tissues. While BMP2 expression begins at (pregastrulation) stage 1 in the hypoblast, BMP4 expression commences—distinctly delayed compared to the mouse—diffusely at (pregastrulation) stage 2; from stage 3 onwards, BMP4 is expressed peripherally in hypoblast and epiblast and in the mesoderm at the posterior pole of the embryonic disc. BLIMP1 expression begins throughout the hypoblast at stage 1 and emerges in single primordial germ cell (PGC) precursors in the posterior epiblast at stage 2 and then in single mesoderm cells at positions identical to those identified by PGC-specific antibodies. These expression patterns suggest that function and chronology of factors involved in germline segregation are similar in mouse and rabbit, but higher temporal and spatial resolution offered by the rabbit demonstrates a variable role of bone morphogenetic proteins and makes “blimping” a candidate case for lateral inhibition without the need for an allantoic germ cell niche.

Primordial Germ Cells in Mice

“…The different properties between mouse and non-rodent mammalian ESCs may be a reflection of the presence of different molecular logic in the mechanisms for early development between mouse and non-rodent mammals. It is also of note that the modes of gastrulation, during which PGCs emerge, are different between mice and non-rodent mammals, including humans (Sadler 2010;Hopf et al 2011). It is therefore important to elucidate the process of germ cell specification in other non-rodent mammals that develop similarly to humans, before any rational approach can be devised for differentiating hESCs/iPSCs into germ cells.…”

The transcriptional repressor Blimp-1 acts downstream of BMP signaling to generate primordial germ cells in the cricket Gryllus bimaculatus

“…Blimp-1 orthologs have been identified in many bilaterian animals, including D. melanogaster (Ng et al, 2006;Agawa et al, 2007;Akagi and Ueda, 2011), rabbit (Hopf et al, 2011), D. rerio (Baxendale et al, 2004;Wilm and Solnica-Krezel, 2005), X. laevis (de Souza et al, 1999), salamander (Chatfield et al, 2014), Gallus gallus (Wan et al, 2014), lamprey (Nikitina et al, 2011), sea star (Hinman and Davidson, 2003;Fresques et al, 2014) and sea urchin (Wang et al, 1996;Livi and Davidson, 2006;Fresques et al, 2014). Consistent with evidence from mice, Blimp-1 is widely expressed in a variety of endodermal and/or mesodermal tissues in these animals.…”

Germline development in amniotes: A paradigm shift in primordial germ cell specification

“…This is a more‐than‐justified question if we consider that rodents stand out among mammals for the peculiar shape of the pre‐gastrulating embryo 10, 34. For example, Bmp4 is expressed in the ring of extra‐embryonic ectoderm bordering with the epiblast, but this structure largely developed in rodents does not exist as such in non‐rodents 41. Even in the rodent guinea‐pig ( Cavia porcellus ), the extra‐embryonic ectoderm does not contact directly with the epiblast at the time of PGC induction 10.…”

“…In the rabbit, PG‐2 (a germ cell epitope) and Prdm‐1 expressing cells have been localised at early gastrulation stage in a region identified in the posterior upper layer (epiblast) and mesoderm 41, 52 (Fig. 2B).…”