There is increasing evidence that the FGF family of signaling molecules plays a central role in the regulation of many aspects of vertebrate embryogenesis, and may also play a role in tumorigenesis. Recently, a gene called sprouty (spry), which apparently encodes an inhibitor of FGF function, has been identified in Drosophila melanogaster. We have isolated and begun to characterize two mouse genes, Spry1 and Spry2, that are closely related to Drosophila spry (D-spry). The experiments described here take advantage of recent improvements in transgenic mouse technology to study in detail the functions of these two genes. Advanced gene targeting methods employing both Cre and Flp DNA recombinases will be used to produce an allelic series of mutations at the Spry1 and Spry2 loci, and to obtain tissue-specific knock-outs of these genes. Studies of the mutant animals will be performed to elucidate the specific functions of Spry1 and Spry2 during development, and to investigate their possible function as tumor suppressor genes. In addition, we describe experiments using a gene replacement strategy to explore the uniqueness or equivalent of Spry1 and Spry2 gene functions.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Mammalian Genetics Study Section (MGN)
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University of California San Francisco
Anatomy/Cell Biology
Schools of Medicine
San Francisco
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Schutzman, Jennifer L; Martin, Gail R (2012) Sprouty genes function in suppression of prostate tumorigenesis. Proc Natl Acad Sci U S A 109:20023-8
Tang, Nan; Marshall, Wallace F; McMahon, Martin et al. (2011) Control of mitotic spindle angle by the RAS-regulated ERK1/2 pathway determines lung tube shape. Science 333:342-345
Frank, Matthew J; Dawson, David W; Bensinger, Steven J et al. (2009) Expression of sprouty2 inhibits B-cell proliferation and is epigenetically silenced in mouse and human B-cell lymphomas. Blood 113:2478-87
Metzger, Ross J; Klein, Ophir D; Martin, Gail R et al. (2008) The branching programme of mouse lung development. Nature 453:745-50
Thum, Thomas; Gross, Carina; Fiedler, Jan et al. (2008) MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 456:980-4
Basson, M Albert; Echevarria, Diego; Ahn, Christina Petersen et al. (2008) Specific regions within the embryonic midbrain and cerebellum require different levels of FGF signaling during development. Development 135:889-98
Klein, Ophir D; Minowada, George; Peterkova, Renata et al. (2006) Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signaling. Dev Cell 11:181-90
Calmont, Amelie; Wandzioch, Ewa; Tremblay, Kimberly D et al. (2006) An FGF response pathway that mediates hepatic gene induction in embryonic endoderm cells. Dev Cell 11:339-48
Shim, Katherine (2006) The auditory sensory epithelium: the instrument of sound perception. Int J Biochem Cell Biol 38:1827-33
Basson, M Albert; Akbulut, Simge; Watson-Johnson, Judy et al. (2005) Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction. Dev Cell 8:229-39

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