Ptf1a/Rbpj complex inhibits ganglion cell fate and drives the specification of all horizontal cell subtypes in the chick retina
Ptf1a/Rbpj complex inhibits ganglion cell fate and drives the specification of all horizontal cell subtypes in the chick retina
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DOI：
10.1016/j.ydbio.2011.07.033
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发表时间：
2011-10-15
影响因子：
2.7
通讯作者：
Guillonneau, X.
中科院分区：
文献类型：
--
作者：
Lelievre, E. C.;Lek, M.;Guillonneau, X.
在发育过程中，视网膜的前体细胞产生六种主要类型的神经元和成年视网膜中发现的穆勒神经胶质细胞。胰腺转录因子1亚单位a(Ptf1a)编码小鼠视网膜水平细胞和大多数无长突细胞亚型所必需的碱性-螺旋-环状-螺旋转录因子。Ptf1a调控的基因以及转录辅助因子在视网膜形成过程中对Ptf1a活性的调控一直没有得到很好的研究。利用逆转录病毒介导的基因转移方法，我们报道了Ptf1a足以促进来自视网膜前体细胞的无长突细胞和水平细胞的命运，并抑制视网膜神经节细胞和光感受器的分化。强迫表达Ptf1a后，GABAericH3水平细胞和非GABAericH3水平细胞均被诱导。我们将Ptf1a描述为Atoh7表达的强大、负向调节因子。此外，Ptf1a蛋白的Rbpj相互作用结构域是其对细胞命运指定的影响所必需的。综上所述，这些数据为Ptf1a活性在鸡视网膜早期细胞规格上的分子基础提供了新的见解。(C)2011 Elsevier Inc.保留所有权利。
During development, progenitor cells of the retina give rise to six principal classes of neurons and the Muller glial cells found within the adult retina. The pancreas transcription factor 1 subunit a (Ptf1a) encodes a basic-helix-loop-helix transcription factor necessary for the specification of horizontal cells and the majority of amacrine cell subtypes in the mouse retina. The Ptf1a-regulated genes and the regulation of Ptf1a activity by transcription cofactors during retinogenesis have been poorly investigated. Using a retrovirus-mediated gene transfer approach, we reported that Ptf1a was sufficient to promote the fates of amacrine and horizontal cells from retinal progenitors and inhibit retinal ganglion cell and photoreceptor differentiation in the chick retina. Both GABAergic H1 and non-GABAergic H3 horizontal cells were induced following the forced expression of Ptf1a. We describe Ptf1a as a strong, negative regulator of Atoh7 expression. Furthermore, the Rbpj-interacting domains of Ptf1a protein were required for its effects on cell fate specification. Together, these data provide a novel insight into the molecular basis of Ptf1a activity on early cell specification in the chick retina. (C) 2011 Elsevier Inc. All rights reserved.