Spatial and temporal inhibition of FGFR2b ligands reveals continuous requirements and novel targets in mouse inner ear morphogenesis

Lisa D. Urness; Xiaofen Wang; Huy Doan; Nathan Shumway; C. Albert Noyes; Edgar Gutierrez-Magana; Ree Lu; Suzanne L. Mansour

doi:10.1242/dev.170142

Spatial and temporal inhibition of FGFR2b ligands reveals continuous requirements and novel targets in mouse inner ear morphogenesis

Development ◽

10.1242/dev.170142 ◽

2018 ◽

Vol 145 (24) ◽

pp. dev170142 ◽

Cited By ~ 5

Author(s):

Lisa D. Urness ◽

Xiaofen Wang ◽

Huy Doan ◽

Nathan Shumway ◽

C. Albert Noyes ◽

...

Keyword(s):

Inner Ear ◽

Novel Targets ◽

Temporal Inhibition

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Spatial and temporal inhibition of FGFR2b ligands reveals continuous requirements and novel targets in mouse inner ear morphogenesis

10.1101/430876 ◽

2018 ◽

Author(s):

Lisa D. Urness ◽

Xiaofen Wang ◽

Huy Doan ◽

Nathan Shumway ◽

C. Albert Noyes ◽

...

Keyword(s):

Inner Ear ◽

Signaling Pathways ◽

Candidate Genes ◽

Dominant Negative ◽

Gene Ablation ◽

Inner Ear Development ◽

Otic Placode ◽

Novel Targets ◽

And Function ◽

Temporal Inhibition

ABSTRACTMorphogenesis 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 the otic ganglion and 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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Otoconia formation in the chick embryo

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100076494 ◽

1983 ◽

Vol 41 ◽

pp. 572-573

Author(s):

C.D. Fermin ◽

M. Igarashi

Keyword(s):

Chick Embryo ◽

Inner Ear ◽

Gallus Domesticus ◽

The Body ◽

Abnormal Behavior ◽

Intensive Study ◽

Basic Fuchsin ◽

Gestational Period ◽

Sensory Epithelia ◽

Transmission Electron

Otoconia are microscopic geometric structures that cover the sensory epithelia of the utricle and saccule (gravitational receptors) of mammals, and the lagena macula of birds. The importance of otoconia for maintanance of the body balance is evidenced by the abnormal behavior of species with genetic defects of otolith. Although a few reports have dealt with otoconia formation, some basic questions remain unanswered. The chick embryo is desirable for studying otoconial formation because its inner ear structures are easily accessible, and its gestational period is short (21 days of incubation).The results described here are part of an intensive study intended to examine the morphogenesis of the otoconia in the chick embryo (Gallus- domesticus) inner ear. We used chick embryos from the 4th day of incubation until hatching, and examined the specimens with light (LM) and transmission electron microscopy (TEM). The embryos were decapitated, and fixed by immersion with 3% cold glutaraldehyde. The ears and their parts were dissected out under the microscope; no decalcification was used. For LM, the ears were embedded in JB-4 plastic, cut serially at 5 micra and stained with 0.2% toluidine blue and 0.1% basic fuchsin in 25% alcohol.

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