Narayanan Ramanathan, Pham Linh, Kerimoglu Cemil, Watanabe Takashi, Castro Hernandez Ricardo, Sokpor Godwin, Ulmke Pauline Antonie, Kiszka Kamila A, Tonchev Anton B, Rosenbusch Joachim, Seong Rho H, Teichmann Ulrike, Frahm Jens, Fischer Andre, Bonn Stefan, Stoykova Anastassia, Staiger Jochen F, Tuoc Tran
Institute of Neuroanatomy, University Medical Center, Georg-August-University, 37075 Goettingen, Germany.
German Center for Neurodegenerative Diseases, 37075 Goettingen, Germany.
iScience. 2018 Jun 29;4:109-126. doi: 10.1016/j.isci.2018.05.014. Epub 2018 May 23.
The abundance of basal progenitors (BPs), basal radial glia progenitors (bRGs) and basal intermediate progenitors (bIPs), in primate brain has been correlated to the high degree of cortical folding. Here we examined the role of BAF155, a subunit of the chromatin remodeling BAF complex, in generation of cortical progenitor heterogeneity. The conditional deletion of BAF155 led to diminished bIP pool and increased number of bRGs, due to delamination of apical RGs. We found that BAF155 is required for normal activity of neurogenic transcription factor PAX6, thus controlling the expression of genes that are involved in bIP specification, cell-cell interaction, and establishment of adherens junction. In a PAX6-dependent manner, BAF155 regulates the expression of the CDC42 effector protein CEP4, thereby controlling progenitor delamination. Furthermore, BAF155-dependent chromatin remodeling seems to exert a specific role in the genesis of BPs through the regulation of human RG-specific genes (such as Foxn4) that possibly acquired evolutionary significance.
灵长类动物大脑中基底祖细胞（BPs）、基底放射状胶质祖细胞（bRGs）和基底中间祖细胞（bIPs）的数量与高度的皮质折叠有关。在这里，我们研究了染色质重塑BAF复合物的一个亚基BAF155在产生皮质祖细胞异质性中的作用。BAF155的条件性缺失导致bIP池减少，bRG数量增加，这是由于顶端放射状胶质细胞（RGs）的脱层所致。我们发现，BAF155是神经源性转录因子PAX6正常活性所必需的，从而控制参与bIP特化、细胞间相互作用和黏附连接建立的基因的表达。BAF155以PAX6依赖的方式调节细胞分裂周期蛋白42（CDC42）效应蛋白CEP4的表达，从而控制祖细胞脱层。此外，依赖BAF155的染色质重塑似乎通过调节可能具有进化意义的人类RG特异性基因（如Foxn4）在BPs的发生中发挥特定作用。
