Early microglia progenitors colonize the embryonic CNS via integrin-mediated migration from the pial surface
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.
Authors
- Melanie Boerries (ORCID: https://orcid.org/0000-0002-3670-0602)
- Roman Sankowski (ORCID: https://orcid.org/0000-0001-9215-8021)
- Elisa Nent
- Marco Prinz (ORCID: https://orcid.org/0000-0002-0349-1955)
- Simon Merkt (ORCID: https://orcid.org/0000-0002-8017-4494)
- Tim Lämmermann (ORCID: https://orcid.org/0000-0002-8553-118X)
- Neil Paterson (ORCID: https://orcid.org/0000-0001-9563-5874)
- Alexander Oschwald (ORCID: https://orcid.org/0000-0002-4443-9141)
- Hannah Botterer (ORCID: https://orcid.org/0000-0002-8466-8133)
- Olaf Groß (ORCID: https://orcid.org/0000-0001-8660-3619)
- Oliver Schilling (ORCID: https://orcid.org/0000-0001-7678-7653)
- Katrin Kierdorf (ORCID: https://orcid.org/0000-0002-9272-4780)
- Monique Havermans
- Geoffroy Andrieux (ORCID: https://orcid.org/0000-0002-5389-9481)
- Lukas Amann (ORCID: https://orcid.org/0000-0002-8363-373X)
- Philippe Petry
- Andreas Schlitzer (ORCID: https://orcid.org/0000-0001-7662-3712)
- Thien‐Ly Julia Dinh
- Cylia Crisand
Institutions
- University of Bonn (DE)
- University of Freiburg (DE)
- University Medical Center Freiburg (DE)
- Max Planck Institute of Immunobiology and Epigenetics (DE)
Publication Details
- Journal
- Developmental Cell
- Published
- 2025-09-10
- DOI
- https://doi.org/10.1016/j.devcel.2025.08.012
- Citations
- 2
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 1.68