Compensational regulation of bHLH transcription factors in the postnatal development of BETA2/NeuroD1-null retina
Compensational regulation of bHLH transcription factors in the postnatal development of BETA2/NeuroD1-null retina
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DOI：
10.1016/j.mod.2007.06.001
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发表时间：
2007-08-01
影响因子：
2.6
通讯作者：
Tsai, Kling-Jer
中科院分区：
文献类型：
--
作者：
Cho, Jang-Hyeon;Klein, William H.;Tsai, Kling-Jer
bHLH转录因子BETA21 NeuroD 1对于视网膜中感光细胞的存活是必需的。尽管该基因在整个视网膜中表达，但BETA21 NeuroD 1敲除小鼠仅在视网膜的外核层中显示感光细胞变性;其他视网膜神经元不受影响。以前的研究表明，缺乏三个bHLH基因的视网膜外植体，在内核层的视网膜神经元需要多个bHLH基因的分化和生存。然而，单基因或双基因突变在眼睛发育过程中没有显示出或显示出较小程度的异常，这可能是因为这些基因之间的补偿或合作调节。因为不是所有的无效小鼠生存，直到视网膜是完全组织，没有直接的证据，这一概念已被报道。为了了解bHLH因子在视网膜发育中的调节机制，我们对BETADNeuroD 1基因敲除小鼠进行了详细的分析。BETA2/NeuroD 1在小鼠视网膜的所有3层中表达，包括所有主要类型的神经元。此外，BETADNeuroD 1的无效突变导致内核层中其他bHLH基因Mash 1、Neurogenin 2和Math 3的上调。我们的数据表明，在视网膜发育过程中的bHLH因子之间存在着补偿和交叉调节机制。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
The bHLH transcriptional factor BETA2lNeuroDl is essential for the survival of photoreceptor cells in the retina. Although this gene is expressed throughout the retina, BETA21NeuroDl knockout mice show photoreceptor cell degeneration only in the outer nuclear layer of the retina; other retinal neurons are not affected. Previous studies on retina explants lacking three bHLH genes revealed that retinal neurons in the inner nuclear layer require multiple bHLH genes for their differentiation and survival. However, single- or double-gene mutations show no or a lesser degree of abnormalities during eye development, likely because of compensation or cooperative regulation among those genes. Because not all null mice survive until the retina is fully organized, no direct evidence of this concept has been reported. To understand the regulatory mechanisms between bHLH factors in retinal development, we performed a detailed analysis of BETADNeuroD1 knockout mice. BETA2/NeuroD1 was expressed in all 3 layers of the mouse retina, including all major types of neurons. In addition, a null mutation of BETADNeuroDl resulted in up-regulation of other bHLH genes, Mash1, Neurogenin2, and Math3, in the inner nuclear layer. Our data suggest that compensatory and cross regulatory mechanisms exist among the bHLH factors during retinal development. (c) 2007 Elsevier Ireland Ltd. All rights reserved.