Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signaling.
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.
Klein
Ophir D
OD
Department of Anatomy and Program in Developmental Biology, School of Medicine, University of California, San Francisco, San Francisco, California 94143,USA.
Minowada
George
G
Peterkova
Renata
R
Kangas
Aapo
A
Yu
Benjamin D
BD
Lesot
Herve
H
Peterka
Miroslav
M
Jernvall
Jukka
J
Martin
Gail R
GR
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D003970:Diastema / Q000196:embryology*; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors* / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008648:Mesoderm / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014070:Tooth / Q000196:embryology* / Q000254:growth & development
D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; C499037:Spry4 protein, mouse; D005346:Fibroblast Growth Factors; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse