McKenna William L, Ortiz-Londono Christian F, Mathew Thomas K, Hoang Kendy, Katzman Sol, Chen Bin
Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, CA 95064;
Department of Bioengineering, University of California, Santa Cruz, CA 95064.
Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):11702-7. doi: 10.1073/pnas.1504144112. Epub 2015 Aug 31.
Generation of distinct cortical projection neuron subtypes during development relies in part on repression of alternative neuron identities. It was reported that the special AT-rich sequence-binding protein 2 (Satb2) is required for proper development of callosal neuron identity and represses expression of genes that are essential for subcerebral axon development. Surprisingly, Satb2 has recently been shown to be necessary for subcerebral axon development. Here, we unravel a previously unidentified mechanism underlying this paradox. We show that SATB2 directly activates transcription of forebrain embryonic zinc finger 2 (Fezf2) and SRY-box 5 (Sox5), genes essential for subcerebral neuron development. We find that the mutual regulation between Satb2 and Fezf2 enables Satb2 to promote subcerebral neuron identity in layer 5 neurons, and to repress subcerebral characters in callosal neurons. Thus, Satb2 promotes the development of callosal and subcerebral neurons in a cell context-dependent manner.
在发育过程中，不同皮质投射神经元亚型的产生部分依赖于对其他神经元身份的抑制。据报道，富含特殊AT序列结合蛋白2（Satb2）对于胼胝体神经元身份的正常发育是必需的，并且抑制对大脑下轴突发育至关重要的基因的表达。令人惊讶的是，最近研究表明Satb2对于大脑下轴突发育也是必需的。在此，我们揭示了这一矛盾背后先前未被识别的机制。我们发现SATB2直接激活前脑胚胎锌指蛋白2（Fezf2）和SRY盒5（Sox5）的转录，这两个基因对大脑下神经元发育至关重要。我们发现Satb2和Fezf2之间的相互调节使Satb2能够促进第5层神经元中的大脑下神经元身份，并抑制胼胝体神经元中的大脑下特征。因此，Satb2以细胞背景依赖的方式促进胼胝体和大脑下神经元的发育。
