Morphogenesis of the inner ear epithelium requires coordinated deployment of several signaling pathways, and disruptions cause abnormalities of hearing and/or balance. The FGFR2b ligands, FGF3 and FGF10, are expressed throughout otic development and are required individually for normal morphogenesis, but their prior and redundant roles in otic placode induction complicates investigation of subsequent combinatorial functions in morphogenesis. To interrogate these roles and identify new effectors of FGF3 and FGF10 signaling at the earliest stages of otic morphogenesis, we used conditional gene ablation after otic placode induction, and temporal inhibition of signaling with a secreted, dominant-negative FGFR2b ectodomain. We show that both ligands are required continuously after otocyst formation for maintenance of otic neuroblasts and for patterning and proliferation of the epithelium, leading to normal morphogenesis of both the cochlear and vestibular domains. Furthermore, the first genomewide identification of proximal targets of FGFR2b signaling in the early otocyst reveals novel candidate genes for inner ear development and function.
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RESEARCH ARTICLE|
01 January 2018
Spatial and temporal inhibition of FGFR2b ligands reveals continuous requirements and novel targets in mouse inner ear morphogenesis
Lisa D. Urness,
Lisa D. Urness
*
1
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA
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Xiaofen Wang,
Xiaofen Wang
*
1
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA
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Huy Doan,
Huy Doan
*
1
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA
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Nathan Shumway,
Nathan Shumway
1
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA
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C. Albert Noyes,
C. Albert Noyes
1
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA
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Edgar Gutierrez-Magana,
Edgar Gutierrez-Magana
1
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA
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Ree Lu,
Ree Lu
1
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA
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Suzanne L. Mansour
Suzanne L. Mansour
#
1
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA
2
Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112-5330, USA
#Author for correspondence: suzi.mansour@genetics.utah.edu
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Lisa D. Urness
*
1
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA
Xiaofen Wang
*
1
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA
Huy Doan
*
1
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA
Nathan Shumway
1
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA
C. Albert Noyes
1
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA
Edgar Gutierrez-Magana
1
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA
Ree Lu
1
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA
Suzanne L. Mansour
#
1
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA
2
Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112-5330, USA
#Author for correspondence: suzi.mansour@genetics.utah.edu
*
contributed equally
Received:
17 Jul 2018
Accepted:
19 Nov 2018
Online ISSN: 1477-9129
Print ISSN: 0950-1991
National Science Foundation
(Graduate Research Fellowship)
National Institutes of Health
(1R01DE025222)
Development dev.170142.
Article history
Received:
17 Jul 2018
Accepted:
19 Nov 2018
Currently Viewing Accepted Manuscript - Newer Version Available
18 Dec 2018
Citation
Lisa D. Urness, Xiaofen Wang, Huy Doan, Nathan Shumway, C. Albert Noyes, Edgar Gutierrez-Magana, Ree Lu, Suzanne L. Mansour; Spatial and temporal inhibition of FGFR2b ligands reveals continuous requirements and novel targets in mouse inner ear morphogenesis. Development 2018; dev.170142. doi: https://doi.org/10.1242/dev.170142
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