| First Author | Biswas S | Year | 2022 |
| Journal | Development | Volume | 149 |
| Issue | 17 | PubMed ID | 36098369 |
| Mgi Jnum | J:330243 | Mgi Id | MGI:7341644 |
| Doi | 10.1242/dev.200610 | Citation | Biswas S, et al. (2022) Mural Wnt/beta-catenin signaling regulates Lama2 expression to promote neurovascular unit maturation. Development 149(17):dev200610 |
| abstractText | Neurovascular unit and barrier maturation rely on vascular basement membrane (vBM) composition. Laminins, a major vBM component, are crucial for these processes, yet the signaling pathway(s) that regulate their expression remain unknown. Here, we show that mural cells have active Wnt/beta-catenin signaling during central nervous system development in mice. Bulk RNA sequencing and validation using postnatal day 10 and 14 wild-type versus adenomatosis polyposis coli downregulated 1 (Apcdd1-/-) mouse retinas revealed that Lama2 mRNA and protein levels are increased in mutant vasculature with higher Wnt/beta-catenin signaling. Mural cells are the main source of Lama2, and Wnt/beta-catenin activation induces Lama2 expression in mural cells in vitro. Markers of mature astrocytes, including aquaporin 4 (a water channel in astrocyte endfeet) and integrin-alpha6 (a laminin receptor), are upregulated in Apcdd1-/- retinas with higher Lama2 vBM deposition. Thus, the Wnt/beta-catenin pathway regulates Lama2 expression in mural cells to promote neurovascular unit and barrier maturation. |
