000114806 001__ 114806
000114806 005__ 20181203021030.0
000114806 0247_ $$2doi$$a10.1038/ncb890
000114806 037__ $$aARTICLE
000114806 245__ $$aExtraembryonic proteases regulate Nodal signalling during gastrulation
000114806 269__ $$a2002
000114806 260__ $$c2002
000114806 336__ $$aJournal Articles
000114806 500__ $$aDevelopmental Biology Group, Swiss Institute for Experimental Cancer Research (ISREC), Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland.
000114806 520__ $$aDuring gastrulation, a cascade of inductive tissue interactions converts pre-existing polarity in the mammalian embryo into antero-posterior pattern. This process is triggered by Nodal, a protein related to transforming growth factor-beta (TFG-beta) that is expressed in the epiblast and visceral endoderm, and its co-receptor Cripto, which is induced downstream of Nodal. Here we show that the proprotein convertases Spc1 and Spc4 (also known as Furin and Pace4, respectively) are expressed in adjacent extraembryonic ectoderm. They stimulate Nodal maturation after its secretion and are required in vivo for Nodal signalling. Embryo explants deprived of extraembryonic ectoderm phenocopy Spc1(-/-); Spc4(-/-) double mutants in that endogenous Nodal fails to induce Cripto. But recombinant mature Nodal, unlike uncleaved precursor, can efficiently rescue Cripto expression. Cripto is also expressed in explants treated with bone morphogenetic protein 4 (BMP4). This indicates that Nodal may induce Cripto through both a signalling pathway in the embryo and induction of Bmp4 in the extraembryonic ectoderm. A lack of Spc1 and Spc4 affects both pathways because these proteases also stimulate induction of Bmp4.
000114806 700__ $$aBeck, S.
000114806 700__ $$aLe Good, J. A.
000114806 700__ $$aGuzman, M.
000114806 700__ $$aBen Haim, N.
000114806 700__ $$aRoy, K.
000114806 700__ $$0240256$$aBeermann, F.$$g169239
000114806 700__ $$0240275$$aConstam, D. B.$$g168579
000114806 773__ $$j4$$k12$$q981-5$$tNat Cell Biol
000114806 909C0 $$0252098$$pUPCDA$$xU11161
000114806 909C0 $$0252092$$pGR-BEERMANN$$xU11779
000114806 909CO $$ooai:infoscience.tind.io:114806$$pSV$$particle
000114806 937__ $$aUPCDA-ARTICLE-2002-001
000114806 973__ $$aOTHER$$rREVIEWED$$sPUBLISHED
000114806 980__ $$aARTICLE