Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signaling.

Abstract	Unlike humans, who have a continuous row of teeth, mice have only molars and incisors separated by a toothless region called a diastema. Although tooth buds form in the embryonic diastema, they regress and do not develop into teeth. Here, we identify members of the Sprouty (Spry) family, which encode negative feedback regulators of fibroblast growth factor (FGF) and other receptor tyrosine kinase signaling, as genes that repress diastema tooth development. We show that different Sprouty genes are deployed in different tissue compartments--Spry2 in epithelium and Spry4 in mesenchyme--to prevent diastema tooth formation. We provide genetic evidence that they function to ensure that diastema tooth buds are refractory to signaling via FGF ligands that are present in the region and thus prevent these buds from engaging in the FGF-mediated bidirectional signaling between epithelium and mesenchyme that normally sustains tooth development.
Authors	Ophir D Klein, George Minowada, Renata Peterkova, Aapo Kangas, Benjamin D Yu, Herve Lesot, Miroslav Peterka, Jukka Jernvall, Gail R Martin
Journal	Developmental cell (Dev Cell) Vol. 11 Issue 2 Pg. 181-90 (Aug 2006) ISSN: 1534-5807 [Print] United States
PMID	16890158 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Adaptor Proteins, Signal Transducing Intracellular Signaling Peptides and Proteins Membrane Proteins Nerve Tissue Proteins Proteins Spry4 protein, mouse Fibroblast Growth Factors Protein Serine-Threonine Kinases Spry2 protein, mouse
Topics	Adaptor Proteins, Signal Transducing Animals Diastema (embryology) Epithelium (drug effects, physiology) Fibroblast Growth Factors (antagonists & inhibitors, physiology) Intracellular Signaling Peptides and Proteins Membrane Proteins Mesoderm (drug effects, physiology) Mice Mice, Inbred C57BL Mice, Knockout Nerve Tissue Proteins (genetics, pharmacology, physiology) Protein Serine-Threonine Kinases Proteins (genetics, pharmacology, physiology) Signal Transduction (drug effects, physiology) Tooth (embryology, growth & development)

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