Tfap2a and 2b act downstream of Ptf1a to promote amacrine cell differentiation during retinogenesis.
Tfap2a and 2b act downstream of Ptf1a to promote amacrine cell differentiation during retinogenesis.
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TFAP2A和2B在PTF1A的下游作用，以促进视网膜生成过程中的无链氨酸细胞分化。
DOI：
10.1186/s13041-015-0118-x
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发表时间：
2015-05-13
期刊：
影响因子：
3.6
通讯作者：
Xiang M
中科院分区：
文献类型：
--
作者：
Jin K;Jiang H;Xiao D;Zou M;Zhu J;Xiang M
视网膜发生是一个精确控制的发育过程，在这个过程中，在内在和外在因素的影响下，会产生不同类型的神经元和神经胶质细胞。三种转录因子FOXN4、RoRβ1及其下游效应因子Ptf1a对无长突细胞和水平细胞的分化起着不可或缺的内在调节作用。然而，目前还不清楚Ptf1a如何从有能力的视网膜前体细胞中指定这两个细胞的命运。在这里，通过结合生物信息学、分子和遗传学的方法，我们在小鼠视网膜中确定了TFAP2a和Tfap2b转录因子是Ptf1a的两个主要下游效应因子。RNA-seq和免疫标记分析表明，在Ptf1a缺失突变的视网膜中，TFAP2a和2b的转录本和蛋白的表达显著下调。它们的过表达能够促进甘氨酸能和GABA能的无长突细胞的分化，而与错误表达的Ptf1a一样，以牺牲光受体为代价，而它们的同时被敲除则具有相反的效果。鉴于水平细胞分化需要TFAP2a和2b，因此我们的研究定义了FOXN4/RoRβ1-PTF1a-TFAP2a/2b转录调控级联，它是无长突细胞和水平细胞在视网膜发育过程中能力、规格和分化的基础。本文的在线版本(doi：10.1186/s13041-0150118-x)包含补充材料，授权用户可以使用。
Retinogenesis is a precisely controlled developmental process during which different types of neurons and glial cells are generated under the influence of intrinsic and extrinsic factors. Three transcription factors, Foxn4, RORβ1 and their downstream effector Ptf1a, have been shown to be indispensable intrinsic regulators for the differentiation of amacrine and horizontal cells. At present, however, it is unclear how Ptf1a specifies these two cell fates from competent retinal precursors. Here, through combined bioinformatic, molecular and genetic approaches in mouse retinas, we identify the Tfap2a and Tfap2b transcription factors as two major downstream effectors of Ptf1a. RNA-seq and immunolabeling analyses show that the expression of Tfap2a and 2b transcripts and proteins is dramatically downregulated in the Ptf1a null mutant retina. Their overexpression is capable of promoting the differentiation of glycinergic and GABAergic amacrine cells at the expense of photoreceptors much as misexpressed Ptf1a is, whereas their simultaneous knockdown has the opposite effect. Given the demonstrated requirement for Tfap2a and 2b in horizontal cell differentiation, our study thus defines a Foxn4/RORβ1-Ptf1a-Tfap2a/2b transcriptional regulatory cascade that underlies the competence, specification and differentiation of amacrine and horizontal cells during retinal development. The online version of this article (doi:10.1186/s13041-015-0118-x) contains supplementary material, which is available to authorized users.
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影响因子：
16.2
作者：
Li, SG;Mo, ZQ;Xiang, MQ
通讯作者：
Xiang, MQ
影响因子：
2.7
作者：
Lelievre, E. C.;Lek, M.;Guillonneau, X.
通讯作者：
Guillonneau, X.
影响因子：
4.6
作者：
Glasgow, SM;Henkel, RM;Johnson, JE
通讯作者：
Johnson, JE
DOI：
10.1073/pnas.1115767109
发表时间：
2012-02-28
影响因子：
11.1
作者：
Luo, Huijun;Jin, Kangxin;Xiang, Mengqing
通讯作者：
Xiang, Mengqing
影响因子：
30.8
作者：
Kawaguchi, Y;Cooper, B;Wright, CVE
通讯作者：
Wright, CVE