Blimp1 regulates development of the posterior forelimb, caudal pharyngeal arches, heart and sensory vibrissae in mice

Abstract

The zinc-finger transcriptional repressor Blimp1 (Prdm1) controls gene expression patterns during differentiation of B lymphocytes and regulates epigenetic changes required for specification of primordial germ cells. Blimp1 is dynamically expressed at diverse tissue sites in the developing mouse embryo, but its functional role remains unknown because Blimp1 mutant embryos arrest at E10.5 due to placental insufficiency. To explore Blimp1 activities at later stages in the embryo proper, here we used a conditional inactivation strategy. A Blimp1-Cre transgenic strain was also exploited to generate a fate map of Blimp1-expressing cells. Blimp1 plays essential roles in multipotent progenitor cell populations in the posterior forelimb, caudal pharyngeal arches, secondary heart field and sensory vibrissae and maintains key signalling centres at these diverse tissues sites. Interestingly, embryos carrying a hypomorphic Blimp1 gfp reporter allele survive to late gestation and exhibit similar, but less severe developmental abnormalities, whereas transheterozygous Blimp1 gfp/-embryos with further reduced expression levels, display exacerbated defects. Collectively, the present experiments demonstrate that Blimp1 requirements in diverse cell types are exquisitely dose dependent.

Identification and expression profiles of prdm1 in medaka Oryzias latipes

“…However, no observation of prdm1a was in the primordial germ cells (PGCs) of medaka. These results hinted that medaka Prdm1a possibly has similar function as its homologues of zebrafish and mouse in development of muscle [38,46], neural crest [41,46], branchial arches [46], fin [43,44,46], eye [29,55], intestine [30,31], heart [28] and bone [56]. In mouse, Prdm1 plays its role itself and/or through its partner factors, Prmt5 and/or Groucho proteins [9,25].…”

“…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].…”

PRDM1 (PR domain containing 1, with ZNF domain)

“…Blimp-1 specifies cell fate of primordial germ cells (Vincent et al, 2005), neural crests and neuron progenitors (Roy and Ng, 2004), and also muscle fiber identity (Baxendale et al, 2004;Hofsten et al, 2008). Blimp-1 is also critical for the normal development of the cardiovascular system, forelimbs and vibrissae (Robertson et al, 2007).…”

Conditional Inactivation of Blimp1 in Adult Mice Promotes Increased Bone Mass

“…Blimp1 is also highly expressed in the intestinal epithelium until the suckling to weaning transition and controls epithelial maturation in mice (15,16). Several inactivation models have been applied to investigate Blimp1 function (7,9,(11)(12)(13)(14)(15)(16)(17); however, the inducible inactivation model at an adult stage has not well been documented. Inactivation of Blimp1 at an adult stage would reveal whether it represents an appropriate target to develop Blimp1-inhibiting reagents to treat adult diseases such as osteoporosis.…”