Blimp1 SuppressesChx10Expression in Differentiating Retinal Photoreceptor Precursors to Ensure Proper Photoreceptor Development
Copyright policy )Blimp1 SuppressesChx10Expression 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. AlthoughBlimp1expression in developing retinal photoreceptor cells has been reported, its function remains unclear. We identifiedBlimp1as a downstream factor of Otx2, which plays an essential role in photoreceptor cell fate determination. To investigate Blimp1 function in the mouse retina, we ablatedBlimp1in the developing retina by conditional gene targeting. In theBlimp1conditional 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 ofBlimp1byin vivoelectroporation suppressed bipolar cell genesis in the developing retina. Multiple genes involved in bipolar development, includingChx10, were upregulated in theBlimp1CKO retina. Furthermore, we showed that Blimp1 can bind to theChx10enhancer and repressChx10enhancer 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.
Homeodomain Proteins, Mice, Knockout, Retinal Bipolar Cells, Stem Cells, Models, Neurological, Gene Expression Regulation, Developmental, Cell Count, Cell Differentiation, Retina, Mice, Electroporation, Gene Targeting, Retinal Cone Photoreceptor Cells, Animals, Cell Lineage, Positive Regulatory Domain I-Binding Factor 1, RNA, Messenger, Oligonucleotide Array Sequence Analysis, Photoreceptor Cells, Vertebrate, Transcription Factors
Homeodomain Proteins, Mice, Knockout, Retinal Bipolar Cells, Stem Cells, Models, Neurological, Gene Expression Regulation, Developmental, Cell Count, Cell Differentiation, Retina, Mice, Electroporation, Gene Targeting, Retinal Cone Photoreceptor Cells, Animals, Cell Lineage, Positive Regulatory Domain I-Binding Factor 1, RNA, Messenger, Oligonucleotide Array Sequence Analysis, Photoreceptor Cells, Vertebrate, Transcription Factors
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