title: Nodal signaling from the visceral endoderm is required to maintain Nodal gene expression in the epiblast and drive DVE/AVE migration.
abstract: In the early mouse embryo, a specialized population of extraembryonic visceral endoderm (VE) cells called the distal VE (DVE) arises at the tip of the egg cylinder stage embryo and then asymmetrically migrates to the prospective anterior, recruiting additional distal cells. Upon migration these cells, called the anterior VE (AVE), establish the anterior posterior (AP) axis by restricting gastrulation-inducing signals to the opposite pole. The Nodal-signaling pathway has been shown to have a critical role in the generation and migration of the DVE/AVE. The Nodal gene is expressed in both the VE and in the pluripotent epiblast, which gives rise to the germ layers. Previous findings have provided conflicting evidence as to the relative importance of Nodal signaling from the epiblast vs. VE for AP patterning. Here we show that conditional mutagenesis of the Nodal gene specifically within the VE leads to reduced Nodal expression levels in the epiblast and incomplete or failed DVE/AVE migration. These results support a required role for VE Nodal to maintain normal levels of expression in the epiblast, and suggest signaling from both VE and epiblast is important for DVE/AVE migration.
authors.affiliation: Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, National Institutes of Health, United States.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Laboratory Animal Sciences Program, SAIC-Frederick, Frederick, MD 21702, United States.
authors.forename: Margaret
authors.initials: M
authors.lastname: Lualdi
authors.affiliation: Department of Pediatrics (Neonatology), The University of Utah, Salt Lake City, UT 84112, United States.
authors.forename: George T
authors.initials: GT
authors.lastname: Lyozin
authors.affiliation: Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, National Institutes of Health, United States.
authors.forename: Prashant
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, National Institutes of Health, United States.
authors.forename: Jadranka
authors.initials: J
authors.lastname: Loncarek
authors.affiliation: Cancer Science Institute of Singapore, Singapore 117599, Singapore.
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Fu
authors.affiliation: Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, National Institutes of Health, United States. Electronic address: mkuehn@mail.nih.gov.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kuehn
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D004707:Endoderm / Q000166:cytology / Q000502:physiology*; D005697:Galactosides; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D017930:Genes, Reporter / Q000235:genetics; D005855:Germ Layers / Q000378:metabolism*; D017403:In Situ Hybridization; D007211:Indoles; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D016296:Mutagenesis; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D005697:Galactosides; D007211:Indoles; D055457:Nodal Protein; C526008:Nodal protein, mouse; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside
keywords: DVE/AVE; Epiblast; Nodal signaling; Ttr-Cre; Visceral endoderm