| First Author | Dudiki T | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 986 |
| PubMed ID | 32080187 | Mgi Jnum | J:286726 |
| Mgi Id | MGI:6401752 | Doi | 10.1038/s41467-020-14787-y |
| Citation | Dudiki T, et al. (2020) Microglia control vascular architecture via a TGFbeta1 dependent paracrine mechanism linked to tissue mechanics. Nat Commun 11(1):986 |
| abstractText | Tissue microarchitecture and mechanics are important in development and pathologies of the Central Nervous System (CNS); however, their coordinating mechanisms are unclear. Here, we report that during colonization of the retina, microglia contacts the deep layer of high stiffness, which coincides with microglial bipolarization, reduction in TGFbeta1 signaling and termination of vascular growth. Likewise, stiff substrates induce microglial bipolarization and diminish TGFbeta1 expression in hydrogels. Both microglial bipolarization in vivo and the responses to stiff substrates in vitro require intracellular adaptor Kindlin3 but not microglial integrins. Lack of Kindlin3 causes high microglial contractility, dysregulation of ERK signaling, excessive TGFbeta1 expression and abnormally-patterned vasculature with severe malformations in the area of photoreceptors. Both excessive TGFbeta1 signaling and vascular defects caused by Kindlin3-deficient microglia are rescued by either microglial depletion or microglial knockout of TGFbeta1 in vivo. This mechanism underlies an interplay between microglia, vascular patterning and tissue mechanics within the CNS. |
