title: Porcn-dependent Wnt signaling is not required prior to mouse gastrulation.
abstract: In mice and humans the X-chromosomal porcupine homolog (Porcn) gene is required for the acylation and secretion of all 19 Wnt ligands and thus represents a bottleneck for all Wnt signaling. We have generated a mouse line carrying a floxed allele for Porcn and used zygotic, oocyte-specific and visceral endoderm-specific deletions to investigate embryonic and extra-embryonic requirements for Wnt ligand secretion. We show that there is no requirement for Porcn-dependent secretion of Wnt ligands during preimplantation development of the mouse embryo. Porcn-dependent Wnts are first required for the initiation of gastrulation, where Porcn function is required in the epiblast but not the visceral endoderm. Heterozygous female embryos, which are mutant in both trophoblast and visceral endoderm due to imprinted X chromosome inactivation, complete gastrulation but display chorio-allantoic fusion defects similar to Wnt7b mutants. Our studies highlight the importance of Wnt3 and Wnt7b for embryonic and placental development but suggest that endogenous Porcn-dependent Wnt secretion does not play an essential role in either implantation or blastocyst lineage specification.
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, Toronto, ON M5G 1X8, Canada.
authors.forename: Steffen
authors.initials: S
authors.lastname: Biechele
authors.forename: Katie
authors.initials: K
authors.lastname: Cockburn
authors.forename: Fredrik
authors.initials: F
authors.lastname: Lanner
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Cox
authors.forename: Janet
authors.initials: J
authors.lastname: Rossant
mesh_terms: D000217:Acyltransferases; D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D049033:Chorioallantoic Membrane / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D004707:Endoderm / Q000378:metabolism; D054262:Gastrulation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D060508:Wnt3 Protein / Q000235:genetics / Q000378:metabolism; D015053:Zygote / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D060508:Wnt3 Protein; C555508:Wnt3 protein, mouse; C095937:Wnt7b protein, mouse; D000217:Acyltransferases; C491187:Porcn protein, mouse
keywords: Blastocyst; Gastrulation; MBOAT; Porcn; Wnt