Snx3 is important for mammalian neural tube closure via its role in canonical and non-canonical WNT signaling.

ABSTRACT: Disruptions in neural tube (NT) closure result in neural tube defects (NTDs). To understand the molecular processes required for mammalian NT closure, we investigated the role of Snx3, a sorting nexin gene. Snx3-/- mutant mouse embryos display a fully-penetrant cranial NTD. In vivo, we observed decreased canonical WNT target gene expression in the cranial neural epithelium of the Snx3-/- embryos and a defect in convergent extension of the neural epithelium. Snx3-/- cells show decreased WNT secretion, and live cell imaging reveals aberrant recycling of the WNT ligand-binding protein WLS and mis-trafficking to the lysosome for degradation. The importance of SNX3 in WNT signaling regulation is demonstrated by rescue of NT closure in Snx3-/- embryos with a WNT agonist. The potential for SNX3 t

SUBMITTER: Brown HM 

PROVIDER: S-EPMC7687862 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature