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

Abstract : Reg-1α belongs to the Reg family of small, secreted proteins expressed in both pancreas and nervous system. Reg-1α 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-1α to its receptor Extl3 stimulates axonal outgrowth. Reg-1α 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-1α increases migration and differentiation of cultured embryonic rat telencephalic progenitors via the activation of GSK-3β activity. In vivo overexpression of Reg-1α 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-1α effects on cortical neuronal differentiation. We thus conclude that Reg-1α via its proteolytically generated N-terminal domain is required for basic development processes.
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Submitted on : Monday, August 31, 2020 - 5:03:27 PM
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Marjorie Varilh, Acquatella-Tran van Ba, Michelle Silhol, Francisco Nieto-Lopez, Mireille Moussaed, et al.. Reg-1α Promotes Differentiation of Cortical Progenitors via Its N-Terminal Active Domain. Front. Front. Cell Dev. Biol, 2020, 8, Online ahead of print. ⟨10.3389/fcell.2020.00681⟩. ⟨inserm-02926407⟩

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