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Nature and extent of left/right axis defects in T Wis /T Wis mutant mouse embryos
Author(s) -
Concepcion Daniel,
Papaioannou Virginia E.
Publication year - 2014
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.24144
Subject(s) - brachyury , biology , nodal , mutant , notch signaling pathway , gastrulation , genetics , cilium , embryo , locus (genetics) , gene , microbiology and biotechnology , mesoderm , embryogenesis , embryonic stem cell
Background: Mutations in the T‐box gene Brachyury have well known effects on invagination of the endomesodermal layer during gastrulation, but the gene also plays a role in the determination of left/right axis determination that is less well studied. Previous work has implicated node morphology in this effect. We use the T Wis allele of Brachyury to investigate the molecular and morphological effects of the T locus on axis determination in the mouse. Results : Similar to embryos mutant for the T allele, T Wis /T Wis embryos have a high incidence of ventral and/or reversed heart looping. In addition, heterotaxia between the direction of heart looping and the direction of embryo turning is common. Scanning electron microscopy reveals defects in node morphology including irregularity, smaller size, and a decreased number of cilia, although the cilia appear morphologically normal. Molecular analysis shows a loss of perinodal expression of genes involved in Nodal signaling, namely Cer2 , Gdf1 , and Nodal itself. There is also loss of Dll1 expression, a key component of the Notch signaling pathway, in the presomitic mesoderm. Conclusions : Morphological abnormalities of the node as well as disruptions of the molecular cascade of left/right axis determination characterize T Wis /T Wis mutants. Decreased Notch signaling may account for both the morphological defects and the absence of expression of genes in the Nodal signaling pathway. Developmental Dynamics 243:1046–1053, 2014 . © 2014 Wiley Periodicals, Inc.