An FGF signaling loop sustains the generation of differentiated progeny from stem cells in mouse incisors.
Rodent incisors grow throughout adult life, but are prevented from becoming excessively long by constant abrasion, which is facilitated by the absence of enamel on one side of the incisor. Here we report that loss-of-function of sprouty genes, which encode antagonists of receptor tyrosine kinase signaling, leads to bilateral enamel deposition, thus impeding incisor abrasion and resulting in unchecked tooth elongation. We demonstrate that sprouty genes function to ensure that enamel-producing ameloblasts are generated on only one side of the tooth by inhibiting the formation of ectopic ameloblasts from self-renewing stem cells, and that they do so by preventing the establishment of an epithelial-mesenchymal FGF signaling loop. Interestingly, although inactivation of Spry4 alone initiates ectopic ameloblast formation in the embryo, the dosage of another sprouty gene must also be reduced to sustain it after birth. These data reveal that the generation of differentiated progeny from a particular stem cell population can be differently regulated in the embryo and adult.
Klein
Ophir D
OD
Department of Anatomy and Program in Developmental Biology, School of Medicine, University of California at San Francisco, San Francisco, CA 94143-2711, USA.
Lyons
David B
DB
Balooch
Guive
G
Marshall
Grayson W
GW
Basson
M Albert
MA
Peterka
Miroslav
M
Boran
Tomas
T
Peterkova
Renata
R
Martin
Gail R
GR
D048868:Adaptor Proteins, Signal Transducing; D000565:Ameloblasts / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D003743:Dental Enamel / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism; D007180:Incisor / Q000002:abnormalities / Q000166:cytology* / Q000196:embryology*; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D015854:Up-Regulation / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C465570:Shh protein, mouse; C499037:Spry4 protein, mouse; D005346:Fibroblast Growth Factors; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse