Compensatory regulation of the size of the inner ear in response to excess induction of otic progenitors by fibroblast growth factor signaling.
BACKGROUND
The otic placode comprises the progenitors of the inner ear and the neurons that convey hearing and balance information to the brain. Transplantation studies in birds and amphibians demonstrate that when the otic placode is morphologically visible as a thickened patch of ectoderm, it is first committed to an otic fate. Fibroblast growth factor (FGF) signaling initiates induction of the otic placode, and levels of FGF signaling are fine-tuned by the Sprouty family of antagonists of receptor tyrosine kinase signaling.


RESULTS
Here, we examined the size of the otic placode and cup by combinatorial inactivation of the Sprouty1 and Sprouty2 genes. Interestingly, in a Sprouty gene dosage series, early enlargement of the otic placode was progressively restored to normal. Restoration of otic size was preceded by normal levels of FGF signaling, reduced cell proliferation and reduced cell death.


CONCLUSIONS
Our study demonstrates that excess otic placode cells, which form in response to increased FGF signaling, are not maintained in mammals. This suggests that growth plasticity exists in the mammalian otic placode and cup, and that FGF signaling may not be sufficient to induce the genetic program that maintains otic fate.
Department of Pediatrics, Children's Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin.
Jian
J
Zhang
Kevin D
KD
Wright
Amanda A
AA
Mahoney Rogers
Molly M
MM
Barrett
Katherine
K
Shim
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004423:Ear / Q000196:embryology / Q000254:growth & development; D007758:Ear, Inner / Q000196:embryology* / Q000254:growth & development; D004622:Embryo, Mammalian; D004627:Embryonic Induction / Q000235:genetics; D053595:Embryonic Stem Cells / Q000502:physiology*; D051518:Fibroblast Growth Factor 3 / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000502:physiology*; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D010750:Phosphoproteins / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D015398:Signal Transduction / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D051518:Fibroblast Growth Factor 3; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C425468:Spry1 protein, mouse; D005346:Fibroblast Growth Factors; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse
FGF; Sprouty1; Sprouty2; cell death; cell proliferation; gene dosage; induction; inner ear; otic placode