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Early microglia progenitors colonize the embryonic CNS via integrin-mediated migration from the pial surface.

Developmental cell

Authors: Philippe Petry, Alexander Oschwald, Simon Merkt, Thien-Ly Julia Dinh, Geoffroy Andrieux, Cylia Crisand, Hannah Botterer, Elisa Nent, Neil Paterson, Monique Havermans, Roman Sankowski, Oliver Schilling, Melanie Boerries, Lukas Amann, Olaf Groß, Andreas Schlitzer, Marco Prinz, Tim Lämmermann, Katrin Kierdorf

Macrophage progenitors colonize their anatomical niches in the central nervous system (CNS) in distinct pre- and postnatal waves. Microglia progenitors originate from early erythromyeloid progenitors in the yolk sac and enter the murine CNS around embryonic day (E)9.5. While their developmental origin is well established, the molecular mechanisms guiding CNS colonization are not yet resolved. Using transcriptomic and proteomic approaches, we identified potential factors involved in this process. Microglia progenitors showed a distinct integrin surface profile and transmigrate along the extracellular matrix (ECM)-enriched pial surface into the CNS, pointing to a mesenchyme-to-CNS migration route. Loss of the integrin adaptor protein talin-1 in microglia progenitors led to a reduced CNS colonization, whereas macrophage progenitors in the surrounding mesenchyme remained unchanged. Overall, our data suggest that microglial progenitors enter the CNS parenchyma via talin-1-mediated migration from the surrounding mesenchyme through the ECM-enriched pial surface.

Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.

PMID: 40934928

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