Compensatory regulation of the size of the inner ear in response to excess induction of otic progenitors by fibroblast growth factor signaling

Authors

  • Jian Zhang,

    1. Department of Pediatrics, Children's Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin
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  • Kevin D. Wright,

    1. Department of Pediatrics, Children's Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin
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  • Amanda A. Mahoney Rogers,

    1. Department of Pediatrics, Children's Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin
    Current affiliation:
    1. Oakland University William Beaumont School of Medicine, Rochester, MI
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  • Molly M. Barrett,

    1. Department of Pediatrics, Children's Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin
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  • Katherine Shim

    Corresponding author
    1. Department of Pediatrics, Children's Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin
    • Correspondence to: Katherine Shim, Department of Pediatrics, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226. E-mail: kshim@mcw.edu

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Abstract

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. Developmental Dynamics 243:1317–1327, 2014. © 2014 Wiley Periodicals, Inc.

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