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Vol. 12, No. 15, pp. 2332-2344, August 1, 1998
1 Samuel Lunenfeld Research Institute, Mount Sinai
Hospital, Toronto M5G 1X5, Canada;
2 Department of
Molecular & Medical Genetics and Obstetrics & Gynecology,
University of Toronto, Toronto M5S 1A1, Canada
Intercellular communication is needed for both the generation of
the mesodermal germ layer and its division into distinct subpopulations. To dissect the functions of fibroblast growth factor
receptor-1 (FGFR1) during mouse gastrulation as well as to gain
insights into its possible roles during later embryonic development, we
have introduced specific mutations into the Fgfr1 locus by gene
targeting. Our results show functional dominance of one of the receptor
isoforms and suggest a function for the autophosphorylation of site
Y766 in the negative regulation of FGFR1 activity. Y766F and
hypomorphic mutations in Fgfr1 generate opposite phenotypes in
terms of homeotic vertebral transformations, suggesting a role for
FGFR1 in patterning the embryonic anteriorposterior axis by way of
regulation of Hox gene activity.
[Key Words: Fibroblast growth factor; somite; Hox gene; homeotic transformation; limb patterning; phospholipase C]
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