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Ortega, German Camargo; Falk, Sven; Johansson, Pia A.; Peyre, Elise; Broix, Loic; Sahu, Sanjeeb Kumar; Hirst, William; Schlichthaerle, Thomas; Romero, Camino De Juan; Draganova, Kalina; Vinopal, Stanislav; Chinnappa, Kaviya; Gavranovic, Anna; Karakaya, Tugay; Steininger, Thomas; Merl-Pham, Juliane; Feederle, Regina; Shao, Wei; Shi, Song-Hai; Hauck, Stefanie M.; Jungmann, Ralf; Bradke, Frank; Borrell, Victor; Geerlof, Arie; Reber, Simone; Tiwari, Vijay K.; Huttner, Wieland B.; Wilsch-Brauninger, Michaela; Nguyen, Laurent and Götz, Magdalena (2019): The centrosome protein AKNA regulates neurogenesis via microtubule organization. In: Nature, Vol. 567, No. 7746

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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(1) that delaminate and settle in the subventricular zone in enlarged brain regions(2). 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.

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