Overexpression of Leap2 impairsXenopusembryonic development and modulates FGF and activin signals

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HIGHLIGHTSXenopus leap2 is similar to human orthologue and expressed in embryo and adult.FGF, activin and vegT/β-catenin induce leap2 in pluripotent embryonic cells.Leap2 gain of function alters normal embryonic development.Leap2 stimulates FGF signal in embryonic cells but reduces activin signal.LEAP2 impairs migration of HUman Vascular Endothelial Cells (HUVEC).Besides its widely described function in the innate immune response, no other clear physiological function has been attributed so far to the Liver-Expressed-Antimicrobial-Peptide 2 (LEAP2). We used the Xenopus embryo model to investigate potentially new functions for this peptide. We identified the amphibian leap2 gene which is highly related to its mammalian orthologues at both structural and sequence levels. The gene is expressed in the embryo mostly in the endoderm-derived tissues. Accordingly it is induced in pluripotent animal cap cells by FGF, activin or a combination of vegT/β-catenin. Modulating leap2 expression level by gain-of-function strategy impaired normal embryonic development. When overexpressed in pluripotent embryonic cells derived from blastula animal cap explant, leap2 stimulated FGF while it reduced the activin response. Finally, we demonstrate that LEAP2 blocks FGF-induced migration of HUman Vascular Endothelial Cells (HUVEC). Altogether these findings suggest a model in which LEAP2 could act at the extracellular level as a modulator of FGF and activin signals, thus opening new avenues to explore it in relation with cellular processes such as cell differentiation and migration.

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