MassIVE MSV000097998

Partial Public PXD064324

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

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Description

Microglia progenitors initially colonize the developing central nervous system (CNS) around embryonic day (E) 9.5 in the mouse. Even though their ontogeny from early erythromyeloid progenitors in the yolk sac is well defined, the molecular machinery needed to enter the developing CNS is so far not resolved. Here, we combined unbiased transcriptomic and proteomic approaches to screen for potential factors. We identified a distinct and dynamic integrin expression profile on microglial progenitors, whereas in parallel the developing CNS peaks in the production of extracellular matrix (ECM) molecules. We found that this ECM is deposited along the pial surface between CNS and mesenchyme, where microglial progenitors interact with deposited ECM along the barrier zone of the CNS, pointing to a mesenchyme-to-CNS transmigration route of microglial progenitors. Loss of the integrin adaptor molecule Tln1 in microglia progenitors led to a reduced capacity to enter the developing CNS, whereas their numbers in the surrounding mesenchyme remained unchanged. However, deficiency of Itgb1 or Itgb2 alone was not sufficient to affect this migration. Our data revealed an essential role of a complex integrin expression profile on microglia progenitors to equip these cells to interact with ECM at the pial surface of the developing CNS and facilitate their entrance from the surrounding mesenchyme. [doi:10.25345/C5W08WV50] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: microglia, microglia development, microglia progenitor recruitment, macrophage progenitor migration, integrins ; DatasetType:Proteomics

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Principal Investigators:
(in alphabetical order) 		Prof. Dr. Oliver Schilling, Medical Center - University of Freiburg, Germany
Submitting User: oliver_schilling
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