Oron-Karni Varda, Farhy Chen, Elgart Michael, Marquardt Till, Remizova Lena, Yaron Orly, Xie Qing, Cvekl Ales, Ashery-Padan Ruth
Sackler Faculty of Medicine, Human Molecular Genetics and Biochemistry, Tel Aviv University, Ramat Aviv 69978, Tel Aviv, Israel.
European Neuroscience Institute, Developmental Neurobiology Laboratory, University of Göttingen Medical School/Max Planck Society, Grisebachstrasse 5, 37077 Göttingen, Germany.
Development. 2008 Dec;135(24):4037-4047. doi: 10.1242/dev.028308. Epub 2008 Nov 12.
Throughout the developing central nervous system, pre-patterning of the ventricular zone into discrete neural progenitor domains is one of the predominant strategies used to produce neuronal diversity in a spatially coordinated manner. In the retina, neurogenesis proceeds in an intricate chronological and spatial sequence, yet it remains unclear whether retinal progenitor cells (RPCs) display intrinsic heterogeneity at any given time point. Here, we performed a detailed study of RPC fate upon temporally and spatially confined inactivation of Pax6. Timed genetic removal of Pax6 appeared to unmask a cryptic divergence of RPCs into qualitatively divergent progenitor pools. In the more peripheral RPCs under normal circumstances, Pax6 seemed to prevent premature activation of a photoreceptor-differentiation pathway by suppressing expression of the transcription factor Crx. More centrally, Pax6 contributed to the execution of the comprehensive potential of RPCs: Pax6 ablation resulted in the exclusive generation of amacrine interneurons. Together, these data suggest an intricate dual role for Pax6 in retinal neurogenesis, while pointing to the cryptic divergence of RPCs into distinct progenitor pools.
在整个发育中的中枢神经系统中，将脑室区预模式化为离散的神经祖细胞区域是用于以空间协调方式产生神经元多样性的主要策略之一。在视网膜中，神经发生以复杂的时间和空间顺序进行，但尚不清楚视网膜祖细胞（RPC）在任何给定时间点是否表现出内在异质性。在这里，我们对Pax6在时间和空间上受限失活后的RPC命运进行了详细研究。Pax6的定时基因去除似乎揭示了RPC向性质不同的祖细胞池的隐秘分化。在正常情况下，在外围较多的RPC中，Pax6似乎通过抑制转录因子Crx的表达来阻止光感受器分化途径的过早激活。在更靠中心的区域，Pax6有助于RPC综合潜能的发挥：Pax6缺失导致仅产生无长突中间神经元。总之，这些数据表明Pax6在视网膜神经发生中具有复杂的双重作用，同时指出RPC向不同祖细胞池的隐秘分化。
