@article{89bcc7298b594fed8c63445023ba334e,
title = "Microglia maintain structural integrity during fetal brain morphogenesis",
abstract = "Microglia (MG), the brain-resident macrophages, play major roles in health and disease via a diversity of cellular states. While embryonic MG display a large heterogeneity of cellular distribution and transcriptomic states, their functions remain poorly characterized. Here, we uncovered a role for MG in the maintenance of structural integrity at two fetal cortical boundaries. At these boundaries between structures that grow in distinct directions, embryonic MG accumulate, display a state resembling post-natal axon-tract-associated microglia (ATM) and prevent the progression of microcavities into large cavitary lesions, in part via a mechanism involving the ATM-factor Spp1. MG and Spp1 furthermore contribute to the rapid repair of lesions, collectively highlighting protective functions that preserve the fetal brain from physiological morphogenetic stress and injury. Our study thus highlights key major roles for embryonic MG and Spp1 in maintaining structural integrity during morphogenesis, with major implications for our understanding of MG functions and brain development.",
keywords = "microglia, microglial state, development, cerebral cortex, repair, cavity, Spp1, osteopontin, amygdala, corpus callosum",
author = "Lawrence, {Akind{\'e} Ren{\'e}} and Alice Canzi and C{\'e}cile Bridlance and Nicolas Olivi{\'e} and Claire Lansonneur and Clarissa Catale and Lara Pizzamiglio and Benoit Kloeckner and Aymeric Silvin and David Munro and Aur{\'e}lien Fortoul and Davide Boido and Feriel Zehani and Hugues Cartonnet and Sarah Viguier and Guillaume Oller and Paola Squarzoni and Adrien Candat and Julie Helft and C{\'e}cile Allet and Francoise Watrin and Jean-Bernard Manent and Pierre Paoletti and Denis Thieffry and Laura Cantini and Clare Pridans and Josef Priller and Antoinette G{\'e}lot and Paolo Giacobini and Luisa Ciobanu and Florent Ginhoux and Thion, {Morgane Sonia} and Ludmilla Lokmane and Sonia Garel",
note = "Funding Information: We thank M. Keita for excellent technical assistance and E. Touzalin, A. Delecourt, and C. Le Moal for assistance with mouse colonies. We are grateful to Denis Jabaudon and Garel lab members for helpful discussions and critical review of the manuscript, to Ana-Maria Lennon-Dum{\'e}nil, Silvia Cappello, and Cord Brackebusch for the kind gifts of reagents and mouse models, and to Kristine Zengeler and John Lukens for discussions during the course of this work. We thank Lucy Robinson and Ilya Demchenko of Insight Editing London for scientific editing of the manuscript. We thank the IBENS Imaging Facility (France BioImaging, supported by ANR-10-INBS-04, ANR-10-LABX-54 MEMO LIFE, and ANR-11-IDEX-000-02 PSL ∗ Research University, “Investments for the future”) and the midwives of the Gynecology Department, Jeanne de Flandre Hospital of Lille (Centre d{\textquoteright}Orthogenie), for their kind assistance and support. The authors acknowledge the support of the Inserm Cross-Cutting Scientific Program (HuDeCA to P.G.). This work was supported by grants to S.G. from INSERM , CNRS , the ERC Consolidator NImO 616080 , MicroSENSO ANR-19-CE16-0018 , FSER , Fondation du Coll{\`e}ge de France (Fonds St Michel), and Fondation pour la Recherche M{\'e}dicale (FRM) ( EQU202003010195 ). A.R.L. obtained a fellowship from Ecole des Neurosciences de Paris Ile-de-France network and an ATER position from the College de France; C.B. is supported by an AMX PhD fellowship ; N.O. by the FRM (FRM, EQU202003010195 ); C.L. obtained a FRM PhD fellowship (FRM, ECO202006011600 ). Publisher Copyright: {\textcopyright} 2024 The Authors",
year = "2024",
month = feb,
day = "15",
doi = "10.1016/j.cell.2024.01.012",
language = "English",
volume = "187",
pages = "962--980",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}