Atoh1, a basic helix-loop-helix transcription factor (TF), is essential for the differentiation of hair cells (HCs), mechanotransducers that convert sound into auditory signals in the mammalian organ of Corti (OC). Previous work demonstrated that replacing mouse Atoh1 with the fly ortholog atonal rescues HC differentiation, indicating functional replacement by other bHLH genes. However, replacing Atoh1 with Neurog1 resulted in reduced HC differentiation compared to transient Atoh1 expression in a 'self-terminating' Atoh1 conditional null mouse (Atoh1-Cre; Atoh1(f/f)). We now show that combining Neurog1 in one allele with removal of floxed Atoh1 in a 'self-terminating' conditional mutant (Atoh1-Cre; Atoh1(f/kiNeurog1)) mouse results in significantly more differentiated inner HCs and outer HCs that have a prolonged longevity of nine months compared to Atoh1 'self-terminating' littermates. Stereocilia bundles are partially disorganized, disoriented and not HC type specific. Replacement of Atoh1 with Neurog1 maintains limited expression of Pou4f3 and Barhl1 and rescues HCs quantitatively, but not qualitatively. OC patterning as well as supporting cell differentiation is also partially disrupted. Diffusible factors involved in patterning are reduced (Fgf8) and factors involved in cell interactions are changed (Jag1, Hes5). Despite presence of many HCs with stereocilia these mice are deaf, possibly related to HC and OC patterning defects. This study provides a novel approach to disrupt OC development through modulating the HC specific intracellular TF network. The resulting disorganized OC indicates that normally differentiated HCs act as 'self-organizers' for OC development and that Atoh1 plays a critical role to initiate HC stereocilia differentiation independent of HC viability.
Pharmacology, Toxicology and Pharmaceutical Science
2
5%
Mathematics
1
2%
Other
4
9%
Unknown
10
23%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 September 2015.
All research outputs
#5,105,373
of 34,763,505 outputs
Outputs from Development (09501991)
#2,856
of 11,613 outputs
Outputs of similar age
#50,629
of 299,592 outputs
Outputs of similar age from Development (09501991)
#51
of 95 outputs
Altmetric has tracked 34,763,505 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 11,613 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.7. This one has done well, scoring higher than 75% of its peers.
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We're also able to compare this research output to 95 others from the same source and published within six weeks on either side of this one. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.
