Bernadette C. HoldenerBernadette C. HoldenerGenetic analysis of mesoderm induction in mice
During gastrulation, the mammalian embryo undergoes a remarkable transformation.
The definitive germ layers are formed and the basic body plan is established.
The driving force behind this reorganization is the induction of mesoderm.
The broad goal of my research is to understand the mechanisms controlling
mesoderm induction and patterning.To address this goal, I propose to determine
how loss of the mouse mesoderm development gene (msd) gene blocks mesoderm
formation. The mouse msd gene encodes an unknown gene product essential
for mesoderm formation. Embryos lacking the msd gene failto form mesoderm
and die during mid gestation. Gene expression and cell differentiation studies
suggest that the effects of the msd mutation are restricted to primitive
streak formation and mesoderm production (Holdener et al, 1994). Combined,
these results demonstrate a critical role for the msd gene product in early
events required for mammalian mesoderm differentiation. Current efforts
in the lab are focusedon positional cloning the msd gene. In addition, we
are using saturation mutagenesis to generate new alleles and are continuing
to analyze the msd mutant phenotype using in situ hybridization, in vitro
embryo recombination, manipulation of mutant embryonic stem cells and differential
display reverse transcription PCR.Collectively, these studies will help
to determine the mechanism by which mesoderminduction is blocked in msd
mutants and will provide valuable reagents necessaryfor a comprehensive
understanding of this pivotal developmental process.
Holdener, B.C., Thomas, J.W., Schumacher, A., Potter, M. Rinchik, E.M.,
Sharan, S.K., and Magnuson, T. (1995) Localization of eed : A gene required
for axial organization of the mouse embryo. Genomics 27: 447-456. Holdener,
B.C., Rinchik, E.M., and Magnuson, T. (1995) Phenotypic and physical analysis
of an eed allele. Mammalian Genome 6:474-475. Faust, C., Schumacher, A.,
Holdener, B.C., Magnuson, T. (1995)The eed mutation disrupts anterior mesoderm
production in mice. Development 121, 273-285. Thomas, J.W., Holdener, B.C.,
and Magnuson, T. (1994) Sequence analysis of a radiation-induced deletion
breakpoint fusion in mouse. Mammalian Genome 5, 518-519. Holdener, B.C.,
Faust, C.J, Rosenthal, N., and Magnuson, T. (1994) msd is Required for Mesoderm
Induction in Mice. Development. 120, 1335-1346.
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