Blimp1 is a critical determinant of the germ cell lineage in mice

Abstract

Germ cell fate in mice is induced in pluripotent epiblast cells in response to signals from extraembryonic tissues. The specification of approximately 40 founder primordial germ cells and their segregation from somatic neighbours are important events in early development. We have proposed that a critical event during this specification includes repression of a somatic programme that is adopted by neighbouring cells. Here we show that Blimp1 (also known as Prdm1), a known transcriptional repressor, has a critical role in the foundation of the mouse germ cell lineage, as its disruption causes a block early in the process of primordial germ cell formation. Blimp1-deficient mutant embryos form a tight cluster of about 20 primordial germ cell-like cells, which fail to show the characteristic migration, proliferation and consistent repression of homeobox genes that normally accompany specification of primordial germ cells. Furthermore, our genetic lineage-tracing experiments indicate that the Blimp1-positive cells originating from the proximal posterior epiblast cells are indeed the lineage-restricted primordial germ cell precursors.

Identification and expression profiles of prdm1 in medaka Oryzias latipes

“…Except of functions in immune-related cells, Prdm1 plays key roles in the development of a wide variety of tissues in mice [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. In mice, Prdm1 is expressed in endoderm, mesoderm and ectoderm-derived tissues during embryonic development [37].…”

“…In mice, Prdm1 is expressed in endoderm, mesoderm and ectoderm-derived tissues during embryonic development [37]. Prdm1 governs germ cell specification [23][24][25] and regulates development of the sebaceous gland [26], skin epidermis [27], the posterior forelimb, caudal pharyngeal arches, sensory vibrissae, heart [28], photoreceptor [29], and intestine [30,31]. Prdm1 also is a tumor suppressor in blood cells [32][33][34][35] by regulating P53 expression [36].…”

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

“…Between E6.25 and E7.25, the population of Prdm1 ‐expressing pPGCs increases from 6 to about 45, either by proliferation or induction 1, 37. Prdm1 is not an exclusive marker of pPGCs, but is also expressed in the visceral endoderm 37.…”

“…2A) and express both pluripotency and early germline markers. In particular, the nascent PGCs are characterised by the expression of Prdm1 , Prdm14 and Tfap2c (or Ap2γ ), transcription factors required for PGC specification at E7.25 37, 38, 39. Both Prdm1 and Prdm14 seem to be under the direct regulation of the Bmp‐Smad pathway 39 and also under the regulation of the classic mesendodermal marker Brachyury (or T), upregulated by Bmps from the extra‐embryonic regions 40.…”

Genetics of germ cell development

“…18,19 These few cells are recruited from a larger population of cells competent but not destined to form the germline, identified by expression of the transmembrane protein IFITM3 (also called FRAGILIS). 20,21 Recruitment and subsequent induction of germ cell precursors are position-dependent: cells transplanted from distal regions of the epiblast to the proximal-posterior region will form germ cell precursors with approximately equal efficiency as will native proximal epiblast cells.…”