Blimp1 suppresses Chx10 expression in differentiating retinal photoreceptor precursors to ensure proper photoreceptor development.
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.
Katoh
Kimiko
K
Department of Developmental Biology, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan.
Omori
Yoshihiro
Y
Onishi
Akishi
A
Sato
Shigeru
S
Kondo
Mineo
M
Furukawa
Takahisa
T
D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D018274:Electroporation; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D020411:Oligonucleotide Array Sequence Analysis; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000196:embryology / Q000254:growth & development* / Q000502:physiology; D051245:Retinal Bipolar Cells / Q000502:physiology; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D018398:Homeodomain Proteins; C513258:Prdm1 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; C088975:Vsx2 protein, mouse; D000074462:Positive Regulatory Domain I-Binding Factor 1
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