CROCCP2 acts as a human-specific modifier of cilia dynamics and mTOR signaling to promote expansion of cortical progenitors.

Autor:	Van Heurck R; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium; Université Libre de Bruxelles (U.L.B.), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium., Bonnefont J; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium; Université Libre de Bruxelles (U.L.B.), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium., Wojno M; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium; Université Libre de Bruxelles (U.L.B.), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium., Suzuki IK; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium; Université Libre de Bruxelles (U.L.B.), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan., Velez-Bravo FD; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium; Université Libre de Bruxelles (U.L.B.), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium., Erkol E; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium; Université Libre de Bruxelles (U.L.B.), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium., Nguyen DT; Université Libre de Bruxelles (U.L.B.), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium., Herpoel A; Université Libre de Bruxelles (U.L.B.), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium., Bilheu A; Université Libre de Bruxelles (U.L.B.), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium., Beckers S; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium., Ledent C; Université Libre de Bruxelles (U.L.B.), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium., Vanderhaeghen P; VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium; Université Libre de Bruxelles (U.L.B.), Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM), and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium. Electronic address: pierre.vanderhaeghen@kuleuven.be.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2023 Jan 04; Vol. 111 (1), pp. 65-80.e6. Date of Electronic Publication: 2022 Nov 04.
DOI:	10.1016/j.neuron.2022.10.018
Abstrakt:	The primary cilium is a central signaling component during embryonic development. Here we focus on CROCCP2, a hominid-specific gene duplicate from ciliary rootlet coiled coil (CROCC), also known as rootletin, that encodes the major component of the ciliary rootlet. We find that CROCCP2 is highly expressed in the human fetal brain and not in other primate species. CROCCP2 gain of function in the mouse embryonic cortex and human cortical cells and organoids results in decreased ciliogenesis and increased cortical progenitor amplification, particularly basal progenitors. CROCCP2 decreases ciliary dynamics by inhibition of the IFT20 ciliary trafficking protein, which then impacts neurogenesis through increased mTOR signaling. Loss of function of CROCCP2 in human cortical cells and organoids leads to increased ciliogenesis, decreased mTOR signaling, and impaired basal progenitor amplification. These data identify CROCCP2 as a human-specific modifier of cortical neurogenesis that acts through modulation of ciliary dynamics and mTOR signaling. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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