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Cell Stem Cell. 2019 Apr 4;24(4):535-550.e9. doi: 10.1016/j.stem.2019.02.017. Epub 2019 Mar 21.

Neocortical Expansion Due to Increased Proliferation of Basal Progenitors Is Linked to Changes in Their Morphology.

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Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Max Planck Institute for Experimental Medicine, Göttingen, Germany.
Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
Technische Universität Dresden, Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Dresden, Germany.
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany. Electronic address:


The evolutionary expansion of the mammalian neocortex (Ncx) is thought to be linked to increased proliferative capacity of basal progenitors (BPs) and their neurogenic capacity. Here, by quantifying BP morphology in the developing Ncx of mouse, ferret, and human, we show that increased BP proliferative capacity is linked to an increase in BP process number. We identify human membrane-bound PALMDELPHIN (PALMD-Caax) as an underlying factor, and we show that it drives BP process growth and proliferation when expressed in developing mouse and ferret Ncx. Conversely, CRISPR/Cas9-mediated disruption of PALMD or its binding partner ADDUCIN-γ in fetal human Ncx reduces BP process numbers and proliferation. We further show that PALMD-induced processes enable BPs to receive pro-proliferative integrin-dependent signals. These findings provide a link between BP morphology and proliferation, suggesting that changes in BP morphology may have contributed to the evolutionary expansion of the Ncx.


Neurogenesis; Palmd; neocortical development; neocortical expansion; neural progenitor cells; neural progenitor morphology


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