The zinc finger transcriptional repressor Blimp1/Prdm1 is dispensable for early axis formation but is required for specification of primordial germ cells in the mouse

Abstract

Blimp1, a zinc-finger containing DNA-binding transcriptional repressor,functions as a master regulator of B cell terminal differentiation. Considerable evidence suggests that Blimp1 is required for the establishment of anteroposterior axis formation and the formation of head structures during early vertebrate development. In mouse embryos, Blimp1 is strongly expressed in axial mesendoderm, the tissue known to provide anterior patterning signals during gastrulation. Here, we describe for the first time the defects caused by loss of Blimp1 function in the mouse. Blimp1 deficient embryos die at mid-gestation, but surprisingly early axis formation, anterior patterning and neural crest formation proceed normally. Rather, loss of Blimp1 expression disrupts morphogenesis of the caudal branchial arches and leads to a failure to correctly elaborate the labyrinthine layer of the placenta. Blimp1mutant embryos also show widespread blood leakage and tissue apoptosis, and,strikingly, Blimp1 homozygous mutants entirely lack PGCs. At the time of PGC allocation around 7.25 days post coitum, Blimp1 heterozygous embryos exhibit decreased numbers of PCGs. Thus Blimp1 probably acts to turn off the default pathway that allows epiblast cells to adopt a somatic cell fate, and shifts the transcriptional program so that they become exclusively allocated into the germ cell lineage.

Essential Role of Sox2 for the Establishment and Maintenance of the Germ Cell Line

“…They arise as a small subset of cells, in the extraembryonic mesoderm (ExM), at around 7.25 dpc identified by high levels of alkaline phosphatase (APase) activity [11]. The transcriptional regulator Blimp1 (B-lymphocyte-induced maturation protein-1, also known as Prdm1) has been identified as a key factor for the specification of PGCs [12,13]. Gene expression profiling has shown that founder PGCs are characterized by high levels of an interferon-inducible transmembrane protein, fragilis/mil-1/ifitm3 and exclusive expression of a small nuclear Author contributions: S.D.…”

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

“…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.…”