Limited inner ear morphogenesis and neurosensory development are possible in the absence of GATA3

Jeremy S Duncan; Kim-Chew Lim; James D Engel; Bernd Fritzsch

doi:10.1387/ijdb.103178jd

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Limited inner ear morphogenesis and neurosensory development are possible in the absence of GATA3

Journal article

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Limited inner ear morphogenesis and neurosensory development are possible in the absence of GATA3

Jeremy S Duncan, Kim-Chew Lim, James D Engel and Bernd Fritzsch

The International journal of developmental biology, Vol.55(3), pp.297-303

2011

DOI: 10.1387/ijdb.103178jd

PMID: 21553382

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Abstract

Haploinsufficiency of Gata3 causes hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome in mice and humans. Gata3 null mutation leads to early lethality around embryonic day (E)11.5, but catecholamine precursor administration can rescue Gata3 null mutants to E16.5. At E11.5, GATA3 deficiency results in the development of an empty otocyst with an endolymphatic duct. However, using rescued mice we found that some morphogenesis and neurosensory development is possible in the ear without Gata3. Extending previous studies, we find that at E16.5, Gata3 mutant inner ears can undergo partial morphogenesis and develop an endolymphatic duct, a utricular and saccular recess, and a shortened cochlear duct. In addition to the obvious morphogenic aberrations, these studies demonstrate that a subset of neurons develop and connect a fragmented sensory patch of MYO7A-positive hair cells to the vestibular nuclei of the brainstem. In situ hybridization studies reveal altered expression of several transcription factors relevant to ear development and we hypothesize that this may relate to the observed dysmorphia and restricted neurosensory development. While a cochlear duct can form, there is no concurrent cochlear neurosensory development, observations consistent with specific hearing defects encountered by HDR patients and mice with Gata3-associated expression alterations. Gata3 null mutant phenocopies the otic maldevelopment (cochlear duct formation in the absence of neurosensory development) seen in Foxg1cre mediated conditional deletion of microRNA processing enzyme, Dicer1. Finally, while GATA3 is expressed in the developing vestibulo-cochlear efferent (VCE) neurons, and its absence in the null mutants disrupts VCE projections to the ear, loss of GATA3 does not affect VCE progenitor cell migration.

Vestibulocochlear Nerve - metabolism

Catecholamines - administration & dosage

Ear, Inner - embryology

Neurosecretory Systems - embryology

GATA3 Transcription Factor - deficiency

DNA-Binding Proteins - genetics

Hair Cells, Vestibular - physiology

Mice, Knockout

DNA-Binding Proteins - metabolism

Ear, Inner - metabolism

Animals

Cochlear Duct - abnormalities

Hair Cells, Vestibular - cytology

Gene Expression Regulation, Developmental

Vestibulocochlear Nerve - secretion

Neurosecretory Systems - metabolism

Myosins - metabolism

Mice

Mutation

GATA3 Transcription Factor - metabolism

Catecholamines - pharmacology

Cell Movement

Details

Title: Subtitle: Limited inner ear morphogenesis and neurosensory development are possible in the absence of GATA3
Creators: Jeremy S Duncan - Department of Biology, University of Iowa, Iowa, USA
Kim-Chew Lim
James D Engel
Bernd Fritzsch
Resource Type: Journal article
Publication Details: The International journal of developmental biology, Vol.55(3), pp.297-303
DOI: 10.1387/ijdb.103178jd
PMID: 21553382
NLM abbreviation: Int J Dev Biol
ISSN: 0214-6282
eISSN: 1696-3547
Publisher: Spain
Grant note: R01DC005590 / NIDCD NIH HHS R01 DC005590 / NIDCD NIH HHS P30 DC010362 / NIDCD NIH HHS R01 GM028896 / NIGMS NIH HHS
Language: English
Date published: 2011
Academic Unit: Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
Record Identifier: 9984070280302771

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