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Mural Wnt/β-catenin signaling regulates Lama2 expression to promote neurovascular unit maturation. | LitMetric

AI Article Synopsis

  • Laminins in the vascular basement membrane are essential for neurovascular unit and barrier maturation, but how their expression is regulated is still unclear.
  • Researchers found that Wnt/β-catenin signaling is active in mural cells during the development of the central nervous system in mice, influencing the expression of Laminin A2 (Lama2).
  • Increased Lama2 levels in mutant retinas correlated with higher Wnt/β-catenin signaling, leading to upregulation of markers of mature astrocytes, indicating that this signaling pathway plays a key role in developing the neurovascular unit and its barriers.

Article Abstract

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/β-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/β-catenin signaling. Mural cells are the main source of Lama2, and Wnt/β-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-α6 (a laminin receptor), are upregulated in Apcdd1-/- retinas with higher Lama2 vBM deposition. Thus, the Wnt/β-catenin pathway regulates Lama2 expression in mural cells to promote neurovascular unit and barrier maturation.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9578690PMC
http://dx.doi.org/10.1242/dev.200610DOI Listing

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