International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


Mesdc2: A NOVEL MOLECULE REQUIRED FOR PATTERNING IN THE EARLY MOUSE EMBRYO

Bernadette Holdener
State University of New York at Stony Brook
Dept of Biochemistry & Cell Biology
Stony Brook, NY 11794 USA

Co-Authors: Lee L, Zhang L, Brown K, DeRossi C
Institutions: Dept of Biochemistry and Cell Biology, State University of New York at Stony Brook

Mouse embryos lacking the mesoderm development (mesd) deletion interval fail to form mesoderm or a primitive streak and do not survive to term. Characterization of gene expression in mesd mutant embryos demonstrates that failure to form a primitive streak results from a defect in the proximal epiblast. Further, anterior visceral endoderm and epiblast gene expression is expanded, demonstrating that the establishment of the A/P axis is dependent upon antagonism between head and trunk signals. Transgenic rescue of the mesd phenotype demonstrates that the mesd gene(s) and regulatory elements are entirely contained within a 75 kb BAC clone. Comparative sequence analysis identifies two closely linked candidate genes, Mesdc1 and Mesdc2. Human homologues map to a conserved region on Chromosome 15q and cosegregate with a locus for autosomal dominant nocturnal frontal lobe epilepsy (ENFL2). Both candidate genes are ubiquitously expressed. Protein prediction and immunofluorescence data suggest that Mesdc1 is a nuclear and cytoskeleton-associated protein and that Mesdc2 is a novel ER resident protein. Significantly, the Mesdc2 transgene rescues the early polarity defects in deletion homozygotes. We are currently investigating the role of Mesdc1 later in development. These results suggest that Mesdc2 plays an important role in gastrulation, potentially acting as a molecular chaperone to regulate folding or secretion of critical signaling pathway molecules.


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