Blimp1 SuppressesChx10Expression in Differentiating Retinal Photoreceptor Precursors to Ensure Proper Photoreceptor Development

Abstract

The zinc finger transcription factor Blimp1 plays fundamentally important roles in many cell lineages and in the early development of several cell types, including B and T lymphocytes and germ cells. Although Blimp1 expression in developing retinal photoreceptor cells has been reported, its function remains unclear. We identified Blimp1 as a downstream factor of Otx2, which plays an essential role in photoreceptor cell fate determination. To investigate Blimp1 function in the mouse retina, we ablated Blimp1 in the developing retina by conditional gene targeting. In the Blimp1 conditional knockout (CKO) retina, the number of photoreceptor cells was markedly reduced in the differentiated retina. We found that the numbers of both bipolar-like cells and proliferating retinal cells increased noticeably, with ectopic localizations in the postnatal developing retina. In contrast, a reduction of the number of photoreceptor precursors was observed during development. Forced expression of Blimp1 by in vivo electroporation suppressed bipolar cell genesis in the developing retina. Multiple genes involved in bipolar development, including Chx10, were upregulated in the Blimp1 CKO retina. Furthermore, we showed that Blimp1 can bind to the Chx10 enhancer and repress Chx10 enhancer activity. These results suggest that Blimp1 plays a crucial role in photoreceptor development by repressing genes involved in bipolar cell fate specification and retinal cell proliferation in differentiating photoreceptor precursors.

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].…”

An Essential Role for RAX Homeoprotein and NOTCH–HES Signaling inOtx2Expression in Embryonic Retinal Photoreceptor Cell Fate Determination

“…We recently reported that the absence of BLIMP1, an OTX2 downstream transcription factor, led to an aberrant increase of Chx10 expression in developing photoreceptors (Katoh et al, 2010). In the Rax iCKO retina, Chx10 might be upregulated due to a defect of the OTX2-BLIMP1 pathway.…”

Downregulation of Prdm16 Is Critical for HOXB4-mediated Benign HSC Expansion In Vivo

“…PRDM1 is primarily identified as transcription repressor and it maintains photoreceptor identity and neonatal enterocyte by repressing alternative differentiation programs. [205][206][207][208][209] Even more PRDM1directs and maintains mast cell differentiation through maintaining other differentiation initiation at a repressive state. 210 During plasma cell differentiation PRDM1 directly represses Myc through recruitment of HDACs 211 and represses Ciita through LSD1.…”