Reg-1? Promotes Differentiation of Cortical Progenitors via Its N-Terminal Active Domain.

ABSTRACT: Reg-1? belongs to the Reg family of small, secreted proteins expressed in both pancreas and nervous system. Reg-1? is composed of two domains, an insoluble C-type lectin domain and a short soluble N-terminal peptide, which is released from the molecule upon proteolytic N-terminal processing, although the biological significance of this proteolysis remains unclear. We have previously shown that binding of Reg-1? to its receptor Extl3 stimulates axonal outgrowth. Reg-1? and Extl3 genes are expressed in the developing cortex but their expression decreases in adulthood, pointing to a possible function of this signaling system at the early developmental stages. Here, we demonstrate that recombinant Reg-1? increases migration and differentiation of cultured embryonic rat telencephalic progenitors via the activation of GSK-3? activity. In vivo overexpression of Reg-1? by in utero electroporation, has a similar effect, favoring premature differentiation of cortical progenitors. Notably, the N-terminal soluble domain, but not the C-type lectin domain, is largely responsible for Reg-1? effects on cortical neuronal differentiation. We thus conclude that Reg-1? via its proteolytically generated N-terminal domain is required for basic development processes.

SUBMITTER: Varilh M 

PROVIDER: S-EPMC7443566 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature