Effects of the TWis mutation on notochord formation and mesodermal patterning.
The mouse T (Brachyury) gene is required for early mesodermal patterning. Mice homozygous for mutations in T die at midgestation and display defects in mesodermal tissues such as the notochord, the allantois and the somitic mesoderm. To examine the role of T in patterning of somitic and posterior mesoderm along the anterior-posterior axis, we have examined the expression of a panel of molecular markers normally localized to the sub-set of cell types affected in TWis mutant mice. Through the use of whole-mount antibody double labelling techniques, we have analysed the spatial relationships of distinct mesodermal populations relative to cells expressing the T protein. We have also examined the consequences of the TWis mutation on mesodermal populations recognised by these markers. We demonstrate that TWis homozygous mutants retain the ability to form notochordal precursor cells, as identified both by the T antibody and the expression of sonic hedgehog/vertebrate homolog of hedgehog 1 (Shh/vhh-1) and goosecoid, however, these cells fail to proliferate or differentiate. These early notochordal defects appear to result in aberrant somitic differentiation as revealed by the distribution of mox-1 protein and twist RNA expression. Moreover, twist expression in paraxial mesoderm appears to be dependent on normal T activity, while Shh/vhh-1, goosecoid, mox-1 and cdx-4 are not T dependent. We propose that T is required for the maintenance of notochordal tissue and subsequent signals required for somite differentiation.
Conlon
F L
FL
Department of Molecular Biology, Harvard University, Cambridge, MA 02138, USA.
Wright
C V
CV
Robertson
E J
EJ
D000483:Alleles; D000818:Animals; D015415:Biomarkers; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005314:Embryonic and Fetal Development; D005326:Fetal Proteins / Q000096:biosynthesis* / Q000235:genetics; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009672:Notochord / Q000196:embryology*; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein
D015415:Biomarkers; D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein