Tbx2 is essential for patterning the atrioventricular canal and for morphogenesis of the outflow tract during heart development
Author:
Harrelson Zachary1, Kelly Robert G.1, Goldin Sarah N.1, Gibson-Brown Jeremy J.123, Bollag Roni J.34, Silver Lee M.3, Papaioannou Virginia E.1
Affiliation:
1. Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA 2. Department of Biology, Washington University, St Louis, MO 63130, USA 3. Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA 4. Institute of Molecular Genetics and Development, Medical College of Georgia,Augusta, GA 30912, USA
Abstract
Tbx2 is a member of the T-box transcription factor gene family,and is expressed in a variety of tissues and organs during embryogenesis. In the developing heart, Tbx2 is expressed in the outflow tract, inner curvature, atrioventricular canal and inflow tract, corresponding to a myocardial zone that is excluded from chamber differentiation at 9.5 days post coitus (dpc). We have used targeted mutagenesis in mice to investigate Tbx2 function. Mice heterozygous for a Tbx2 null mutation appear normal but homozygous embryos reveal a crucial role for Tbx2 during cardiac development. Morphological defects are observed in development of the atrioventricular canal and septation of the outflow tract. Molecular analysis reveals that Tbx2 is required to repress chamber differentiation in the atrioventricular canal at 9.5 dpc. Analysis of homozygous mutants also highlights a role for Tbx2 during hindlimb digit development. Despite evidence that TBX2 negatively regulates the cell cycle control genes Cdkn2a, Cdkn2b and Cdkn1a in cultured cells, there is no evidence that loss of Tbx2 function during mouse development results in increased levels of p19ARF, p16INK4a,p15INK4b or p21 expression in vivo, nor is there evidence for a genetic interaction between Tbx2 and p53.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
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