Research Group of Molecular Developmental Neurobiology, Department of Molecular Cell Biology, Max-Planck-Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Dev Cell. 2013 May 13;25(3):256-69. doi: 10.1016/j.devcel.2013.04.005. Epub 2013 May 2.
Increased cortical size is essential to the enhanced intellectual capacity of primates during mammalian evolution. The mechanisms that control cortical size are largely unknown. Here, we show that mammalian BAF170, a subunit of the chromatin remodeling complex mSWI/SNF, is an intrinsic factor that controls cortical size. We find that conditional deletion of BAF170 promotes indirect neurogenesis by increasing the pool of intermediate progenitors (IPs) and results in an enlarged cortex, whereas cortex-specific BAF170 overexpression results in the opposite phenotype. Mechanistically, BAF170 competes with BAF155 subunit in the BAF complex, affecting euchromatin structure and thereby modulating the binding efficiency of the Pax6/REST-corepressor complex to Pax6 target genes that regulate the generation of IPs and late cortical progenitors. Our findings reveal a molecular mechanism mediated by the mSWI/SNF chromatin-remodeling complex that controls cortical architecture.
在哺乳动物进化过程中，皮质尺寸的增加对于灵长类动物智力的增强至关重要。控制皮质大小的机制在很大程度上是未知的。在这里，我们表明哺乳动物 BAF170 是染色质重塑复合物 mSWI/SNF 的一个亚基，是控制皮质大小的内在因素。我们发现条件性缺失 BAF170 通过增加中间祖细胞 (IP) 的池来促进间接神经发生，导致皮质增大，而皮质特异性 BAF170 过表达则导致相反的表型。从机制上讲，BAF170 在 BAF 复合物中与 BAF155 亚基竞争，影响常染色质结构，从而调节 Pax6/REST-corepressor 复合物与 Pax6 靶基因的结合效率，这些基因调节 IP 和晚期皮质祖细胞的产生。我们的发现揭示了一种由 mSWI/SNF 染色质重塑复合物介导的分子机制，该机制控制着皮质结构。
