Tylkowski Marco A, Yang Kefei, Hoyer-Fender Sigrid, Stoykova Anastassia
Research Group of Molecular Developmental Neurobiology, Department Molecular Cell Biology, Max-Planck Institute for Biophysical Chemistry, Am Faßberg 11, 37077, Göttingen, Germany.
Cell Mol Life Sci. 2015 May;72(9):1795-809. doi: 10.1007/s00018-014-1766-1. Epub 2014 Oct 29.
Cortical glutamatergic neurons are generated by radial glial cells (RGCs), specified by the expression of transcription factor (TF) Pax6, in the germinative zones of the dorsal telencephalon. Here, we demonstrate that Pax6 regulates the structural assembly of the interphase centrosomes. In the cortex of the Pax6-deficient Small eye (Sey/Sey) mutant, we find a defect of the appendages of the mother centrioles, indicating incomplete centrosome maturation. Consequently, RGCs fail to generate primary cilia, and instead of staying in the germinative zone for renewal, RGCs detach from the ventricular surface thus affecting the interkinetic nuclear migration and they exit prematurely from mitosis. Mechanistically, we show that TF Pax6 directly regulates the activity of the Odf2 gene encoding for the appendage-specific protein Odf2 with a role for the assembly of mother centriole. Our findings demonstrate a molecular mechanism that explains important characteristics of the centrosome disassembly and malfunctioning in developing cortex lacking Pax6.
皮质谷氨酸能神经元由背侧端脑生发区中表达转录因子（TF）Pax6的放射状胶质细胞（RGC）产生。在此，我们证明Pax6调节间期中心体的结构组装。在Pax6缺陷型小眼（Sey/Sey）突变体的皮质中，我们发现母中心粒附属物存在缺陷，表明中心体成熟不完全。因此，RGC无法产生初级纤毛，RGC没有停留在生发区进行更新，而是从脑室表面脱离，从而影响核内有丝分裂迁移，并且它们过早地退出有丝分裂。从机制上讲，我们表明转录因子Pax6直接调节编码附属物特异性蛋白Odf2的Odf2基因的活性，该蛋白在母中心粒组装中起作用。我们的研究结果证明了一种分子机制，该机制解释了在缺乏Pax6的发育中的皮质中中心体解体和功能异常的重要特征。
