NeuroD factors regulate cell fate and neurite stratification in the developing retina.
NeuroD factors regulate cell fate and neurite stratification in the developing retina.
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DOI：
10.1523/jneurosci.2555-10.2011
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发表时间：
2011-05-18
期刊：
影响因子：
--
通讯作者：
Cepko CL
中科院分区：
文献类型：
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作者：
Cherry TJ;Wang S;Bormuth I;Schwab M;Olson J;Cepko CL
转录因子的碱性螺旋-环-螺旋（bHLH）家族成员已被证明控制许多组织发育的关键方面。为了鉴定可能调节视网膜细胞发育特定方面的bHLH基因，我们研究了bHLH基因在单个发育中的小鼠视网膜细胞中的表达，特别强调了NeuroD家族。其中两个因子，NeuroD 2和NeuroD 6/NEX，以前没有报道在视网膜中表达。进行了一系列功能丧失和获得实验，这表明NeuroD基因在其活性方面既有相似性又有差异。值得注意的是，NeuroD基因的错误表达可以将无长突细胞突起引导到内丛状层中的两到三个特定的亚板层。这种作用对细胞类型和NeuroD基因是特异性的，因为AII无长突细胞类型对NeuroD 1和NeuroD 6的作用是难治的，但对NeuroD 2对神经突靶向的作用是独特敏感的。此外，NeuroD 2在AII无长突细胞等中内源性表达，并且NeuroD 2功能的丧失导致AII无长突细胞的部分丧失。错误表达NeuroD基因对视网膜细胞命运决定的影响也表明了共享和分歧的功能。值得注意的是，即使在神经节细胞发生的正常发育窗口之后，NeuroD 2错误表达也诱导神经节细胞的产生。总之，这些数据表明，NeuroD家族的成员是重要的神经元细胞类型的身份，并可能参与视网膜发育的几个细胞类型的具体方面，包括命运的决定，分化，形态发育和电路的形成。
Members of the basic helix-loop-helix (bHLH) family of transcription factors have been shown to control critical aspects of development in many tissues. To identify bHLH genes that might regulate specific aspects of retinal cell development, we investigated the expression of bHLH genes in single, developing mouse retinal cells, with particular emphasis on the NeuroD family. Two of these factors, NeuroD2 and NeuroD6/NEX, had not been previously reported as expressed in the retina. A series of loss- and gain-of-function experiments was performed, which suggested that NeuroD genes have both similarities and differences in their activities. Notably, misexpression of NeuroD genes can direct amacrine cell processes to two to three specific sublaminae in the inner plexiform layer. This effect is specific to cell type and NeuroD gene, as the AII amacrine cell type is refractory to the effects of NeuroD1 and NeuroD6, but uniquely sensitive to the effect of NeuroD2 on neurite targeting. Additionally, NeuroD2 is endogenously expressed in AII amacrine cells, among others, and loss of NeuroD2 function results in a partial loss of AII amacrine cells. The effects of misexpressing NeuroD genes on retinal cell fate determination also suggested shared and divergent functions. Remarkably, NeuroD2 misexpression induced ganglion cell production even after the normal developmental window of ganglion cell genesis. Together, these data suggest that members of the NeuroD family are important for neuronal cell type identity and may be involved in several cell type-specific aspects of retinal development, including fate determination, differentiation, morphological development, and circuit formation.