Protooncogene Ski cooperates with the chromatin-remodeling factor Satb2 in specifying callosal neurons

作者：Baranek Constanze; Dittrich Manuela; Parthasarathy Srinivas; Bonnon Carine Gaiser; Britanova Olga; Lanshakov Dmitriy; Boukhtouche Fatiha; Sommer Julia E; Colmenares Clemencia; Tarabykin Victor; Atanasoski Suzana^*

来源：Proceedings of the National Academy of Sciences, 2012, 109(9): 3546-3551.

DOI：10.1073/pnas.1108718109

• cortical development
• cell fate
• transcriptional regulation

First insights into the molecular programs orchestrating the progression from neural stem cells to cortical projection neurons are emerging. Loss of the transcriptional regulator Ski has been linked to the human 1p36 deletion syndrome, which includes central nervous system defects. Here, we report critical roles for Ski in the maintenance of the neural stem cell pool and the specification of callosal neurons. Ski-deficient callosal neurons lose their identity and ectopically express the transcription factor Ctip2. The misspecified callosal neurons largely fail to form the corpus callosum and instead redirect their axons toward subcortical targets. We identify the chromatin-remodeling factor Satb2 as a partner of Ski, and show that both proteins are required for transcriptional repression of Ctip2 in callosal neurons. We propose a model in which Satb2 recruits Ski to the Ctip2 locus, and Ski attracts histone deacetylases, thereby enabling the formation of a functional nucleosome remodeling and deacetylase repressor complex. Our findings establish a central role for Ski-Satb2 interactions in regulating transcriptional mechanisms of callosal neuron specification.

• 出版日期2012-2-28