The morphogenetic movements of vertebrate gastrulation and concomitant induction of mesoderm are well characterized in organisms such as Xenopus, chick and mouse. Due to the accessibility and ease of in vitro and in vivo manipulation of the Xenopus embryo, a number of molecules with potential roles in mesoderm induction and organization have been identified. However, one limitation facing experiments with amphibian or chick is the absence of mutations; and in many cases, it is unknown whether these identified molecules are part of an endogenous mesoderm production pathway or if they simply simulate the normal embryonic mesoderm induction mechanism. The ability to induce mutations in the mouse provides an advantage for studying the complex interactions during gastrulation on a defined genetic background. The fate map of the early mouse gastrula is similar to that of Xenopus and chick, and homologues of molecules implicated in Xenopus mesoderm induction are also temporally and spatially expressed during mouse gastrulation. Thus, the underlying control of this process is likely to be conserved amongst vertebrates. The experiments outlined in this proposal focus on a series of radiation- induced deletions which identify through complementation and embryological studies regions of mouse chromosome 7 containing genes needed for gastrulation and mesoderm organization.
The specific aims concentrate on molecular approaches for identifying and evaluating the functional significance of candidate genes as well as a continued analysis of the biology of the mutations.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD024462-09
Application #
2403176
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1989-12-01
Project End
1999-11-30
Budget Start
1997-12-01
Budget End
1998-11-30
Support Year
9
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Genetics
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Richie, Ellen R; Schumacher, Armin; Angel, Joe M et al. (2002) The Polycomb-group gene eed regulates thymocyte differentiation and suppresses the development of carcinogen-induced T-cell lymphomas. Oncogene 21:299-306
Morin-Kensicki, E M; Faust, C; LaMantia, C et al. (2001) Cell and tissue requirements for the gene eed during mouse gastrulation and organogenesis. Genesis 31:142-6
Lessard, J; Schumacher, A; Thorsteinsdottir, U et al. (1999) Functional antagonism of the Polycomb-Group genes eed and Bmi1 in hemopoietic cell proliferation. Genes Dev 13:2691-703
Faust, C; Lawson, K A; Schork, N J et al. (1998) The Polycomb-group gene eed is required for normal morphogenetic movements during gastrulation in the mouse embryo. Development 125:4495-506
van Lohuizen, M; Tijms, M; Voncken, J W et al. (1998) Interaction of mouse polycomb-group (Pc-G) proteins Enx1 and Enx2 with Eed: indication for separate Pc-G complexes. Mol Cell Biol 18:3572-9
Schumacher, A; Lichtarge, O; Schwartz, S et al. (1998) The murine Polycomb-group gene eed and its human orthologue: functional implications of evolutionary conservation. Genomics 54:79-88
Holdener, B C; Brown, S D; Angel, J M et al. (1993) Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 7. Mamm Genome 4 Spec No:S110-20
Faust, C; Magnuson, T (1993) Genetic control of gastrulation in the mouse. Curr Opin Genet Dev 3:491-8
Williams, P T; Krauss, R M; Vranizan, K M et al. (1992) Associations of lipoproteins and apolipoproteins with gradient gel electrophoresis estimates of high density lipoprotein subfractions in men and women. Arterioscler Thromb 12:332-40
Kelsey, G; Schedl, A; Ruppert, S et al. (1992) Physical mapping of the albino-deletion complex in the mouse to localize alf/hsdr-1, a locus required for neonatal survival. Genomics 14:275-87

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