Blimp1 Suppresses Chx10 Expression in Differentiating Retinal Photoreceptor Precursors to Ensure Proper Photoreceptor Development
Blimp1 Suppresses Chx10 Expression in Differentiating Retinal Photoreceptor Precursors to Ensure Proper Photoreceptor Development
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DOI：
10.1523/jneurosci.0771-10.2010
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发表时间：
2010-05-12
影响因子：
5.3
通讯作者：
Furukawa, Takahisa
中科院分区：
文献类型：
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作者：
Katoh, Kimiko;Omori, Yoshihiro;Furukawa, Takahisa
锌指转录因子Blimp 1在许多细胞谱系和几种细胞类型（包括B和T淋巴细胞和生殖细胞）的早期发育中起着根本性的重要作用。虽然Blimp1在视网膜感光细胞发育中的表达已有报道，但其功能尚不清楚。我们确定Blimp1作为Otx 2的下游因子，Otx 2在感光细胞命运决定中起着重要作用。为了研究Blimp1在小鼠视网膜中的功能，我们通过条件基因打靶在发育中的视网膜中消融Blimp1。在Blimp1条件性敲除（CKO）视网膜中，分化的视网膜中感光细胞的数量显著减少。我们发现，双极样细胞和增殖的视网膜细胞的数量显着增加，在出生后发育的视网膜异位定位。相反，在发育过程中观察到感光体前体的数量减少。通过体内电穿孔强制表达Blimp1抑制了发育中视网膜双极细胞的发生。多个基因参与双极发展，包括Chx10，在Blimp1 CKO视网膜上调。此外，我们发现Blimp1可以结合Chx10增强子并抑制Chx10增强子活性。这些结果表明，Blimp1在感光细胞发育中起着至关重要的作用，通过抑制基因参与双极细胞的命运规范和视网膜细胞增殖分化感光细胞前体。
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.