Institute of Stem Cell Research, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany.
Physiological Genomics, Biomedical Center, Ludwig-Maximilians University, Munich, Germany.
Nature. 2019 Mar;567(7746):113-117. doi: 10.1038/s41586-019-0962-4. Epub 2019 Feb 20.
The expansion of brain size is accompanied by a relative enlargement of the subventricular zone during development. Epithelial-like neural stem cells divide in the ventricular zone at the ventricles of the embryonic brain, self-renew and generate basal progenitors that delaminate and settle in the subventricular zone in enlarged brain regions. The length of time that cells stay in the subventricular zone is essential for controlling further amplification and fate determination. Here we show that the interphase centrosome protein AKNA has a key role in this process. AKNA localizes at the subdistal appendages of the mother centriole in specific subtypes of neural stem cells, and in almost all basal progenitors. This protein is necessary and sufficient to organize centrosomal microtubules, and promote their nucleation and growth. These features of AKNA are important for mediating the delamination process in the formation of the subventricular zone. Moreover, AKNA regulates the exit from the subventricular zone, which reveals the pivotal role of centrosomal microtubule organization in enabling cells to both enter and remain in the subventricular zone. The epithelial-to-mesenchymal transition is also regulated by AKNA in other epithelial cells, demonstrating its general importance for the control of cell delamination.
脑容量的扩大伴随着胚胎大脑室管膜下区在发育过程中的相对扩大。上皮样神经干细胞在胚胎大脑室管膜区的脑室中分裂,自我更新并产生基底祖细胞,这些祖细胞在扩大的脑区中分层并定居在室管膜下区。细胞在室管膜下区停留的时间长短对于控制进一步的扩增和命运决定至关重要。在这里,我们表明,有丝分裂中心体蛋白 AKNA 在这个过程中起着关键作用。AKNA 定位于特定类型的神经干细胞和几乎所有基底祖细胞的母中心粒的亚远端附属物上。这种蛋白质对于组织中心体微管、促进其核形成和生长是必需的和充分的。AKNA 的这些特征对于介导室管膜下区形成中的分层过程很重要。此外,AKNA 调节从室管膜下区的退出,这揭示了中心体微管组织在使细胞既能进入又能留在室管膜下区中的关键作用。上皮-间充质转化也被 AKNA 在其他上皮细胞中调控,证明了它对细胞分层控制的普遍重要性。