Journal article
Continued Expression of GATA3 Is Necessary for Cochlear Neurosensory Development
PloS one, Vol.8(4), pp.e62046-e62046
04/16/2013
DOI: 10.1371/journal.pone.0062046
PMCID: PMC3628701
PMID: 23614009
Abstract
Hair cells of the developing mammalian inner ear are progressively defined through cell fate restriction. This process culminates in the expression of the bHLH transcription factor
Atoh1
, which is necessary for differentiation of hair cells, but not for their specification. Loss of several genes will disrupt ear morphogenesis or arrest of neurosensory epithelia development. We previously showed in null mutants that the loss of the transcription factor,
Gata3
, results specifically in the loss of all cochlear neurosensory development. Temporal expression of
Gata3
is broad from the otic placode stage through the postnatal ear. It therefore remains unclear at which stage in development Gata3 exerts its effect. To better understand the stage specific effects of Gata3, we investigated the role of Gata3 in cochlear neurosensory specification and differentiation utilizing a LoxP targeted
Gata3
line and two Cre lines.
Foxg1
Cre
∶Gata3
f/f
mice show recombination of
Gata3
around E8.5 but continue to develop a cochlear duct without differentiated hair cells and spiral ganglion neurons. qRT-PCR data show that
Atoh1
was down-regulated but not absent in the duct whereas other hair cell specific genes such as
Pou4f3
were completely absent. In addition, while
Sox2
levels were lower in the
Foxg1
Cre
:Gata3
f/f
cochlea,
Eya1
levels remained normal. We conclude that Eya1 is unable to fully upregulate
Atoh1 or Pou4f3
, and drive differentiation of hair cells without Gata3.
Pax2-Cre∶Gata3
f/f
mice show a delayed recombination of
Gata3
in the ear relative to
Foxg1
Cre
:Gata3
f/f
. These mice exhibited a cochlear duct containing patches of partially differentiated hair cells and developed only few and incorrectly projecting spiral ganglion neurons. Our conditional deletion studies reveal a major role of Gata3 in the signaling of prosensory genes and in the differentiation of cochlear neurosenory cells. We suggest that Gata3 may act in combination with Eya1, Six1, and Sox2 in cochlear prosensory gene signaling.
Details
- Title: Subtitle
- Continued Expression of GATA3 Is Necessary for Cochlear Neurosensory Development
- Creators
- Jeremy S DuncanBernd Fritzsch
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.8(4), pp.e62046-e62046
- DOI
- 10.1371/journal.pone.0062046
- PMID
- 23614009
- PMCID
- PMC3628701
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; San Francisco, USA
- Alternative title
- GATA3 in Neurosensory Development
- Language
- English
- Date published
- 04/16/2013
- Academic Unit
- Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984070618902771
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