title: Overexpression of Leap2 impairs Xenopus embryonic development and modulates FGF and activin signals.
abstract: 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.
authors.affiliation: Univ. Bordeaux, F-33076 Bordeaux, France; INSERM U1035, F-33076 Bordeaux, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Thiébaud
authors.affiliation: Bordeaux INP, BPRVS, EA4135, F-33000 Bordeaux, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Garbay
authors.affiliation: Univ. Bordeaux, F-33076 Bordeaux, France; INSERM U1035, F-33076 Bordeaux, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Auguste
authors.affiliation: Bordeaux INP, BPRVS, EA4135, F-33000 Bordeaux, France.
authors.forename: Caroline Le
authors.initials: CL
authors.lastname: Sénéchal
authors.affiliation: Univ. Bordeaux, F-33076 Bordeaux, France; INSERM U1035, F-33076 Bordeaux, France.
authors.forename: Zuzanna
authors.initials: Z
authors.lastname: Maciejewska
authors.affiliation: Univ. Bordeaux, F-33076 Bordeaux, France; INSERM U1035, F-33076 Bordeaux, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Fédou
authors.affiliation: Univ. Bordeaux, F-33076 Bordeaux, France; CNRS UMS 3427, F-33076 Bordeaux, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Gauthereau
authors.affiliation: Bordeaux INP, BPRVS, EA4135, F-33000 Bordeaux, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Costaglioli
authors.affiliation: Univ. Bordeaux, F-33076 Bordeaux, France; INSERM U1035, F-33076 Bordeaux, France. Electronic address: Nadine.theze-thiebaud@u-bordeaux.fr.
authors.forename: Nadine
authors.initials: N
authors.lastname: Thézé
mesh_terms: D028341:Activins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism; D001798:Blood Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D015398:Signal Transduction; D014982:Xenopus laevis / Q000235:genetics / Q000254:growth & development; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; C495270:CTNNB1 protein, human; D051176:beta Catenin; C475606:liver-expressed antimicrobial peptide 2, human; D028341:Activins
keywords: Activin; Cell migration; Embryo; FGF; HUVEC; Leap2; Xenopus laevis