Journal article
Understanding Molecular Evolution and Development of the Organ of Corti Can Provide Clues for Hearing Restoration
Integrative and comparative biology, Vol.58(2), pp.351-365
08/2018
DOI: 10.1093/icb/icy019
PMCID: PMC6104702
PMID: 29718413
Abstract
The mammalian hearing organ is a stereotyped cellular assembly with orderly innervation: two types of spiral ganglion neurons (SGNs) innervate two types of differentially distributed hair cells (HCs). HCs and SGNs evolved from single neurosensory cells through gene multiplication and diversification. Independent regulation of HCs and neuronal differentiation through expression of basic helix-loop-helix transcription factors (bHLH TFs:
Atoh1
,
Neurog1
,
Neurod1
) led to the evolution of vestibular HC assembly and their unique type of innervation. In ancestral mammals, a vestibular organ was transformed into the organ of Corti (OC) containing a single row of inner HC (IHC), three rows of outer HCs (OHCs), several unique supporting cell types, and a peculiar innervation distribution. Restoring the OC following long-term hearing loss is complicated by the fact that the entire organ is replaced by a flat epithelium and requires reconstructing the organ from uniform undifferentiated cell types, recapitulating both evolution and development. Finding the right sequence of gene activation during development that is useful for regeneration could benefit from an understanding of the OC evolution. Toward this end, we report on
Foxg1
and
Lmx1a
mutants that radically alter the OC cell assembly and its innervation when mutated and may have driven the evolutionary reorganization of the basilar papilla into an OC in ancestral Therapsids. Furthermore, genetically manipulating the level of bHLH TFs changes HC type and distribution and allows inference how transformation of HCs might have happened evolutionarily. We report on how bHLH TFs regulate OHC/IHC and how misexpression (
Atoh1-Cre
;
Atoh1
f/kiNeurog1
) alters HC fate and supporting cell development. Using mice with altered HC types and distribution, we demonstrate innervation changes driven by HC patterning. Using these insights, we speculate on necessary steps needed to convert a random mixture of post-mitotic precursors into the orderly OC through spatially and temporally regulated critical bHLH genes in the context of other TFs to restore normal innervation patterns.
Details
- Title: Subtitle
- Understanding Molecular Evolution and Development of the Organ of Corti Can Provide Clues for Hearing Restoration
- Creators
- Israt Jahan - Department of Biology, University of Iowa, 129 East Jefferson, Iowa City, IA 52242, USAKaren L Elliott - Department of Biology, University of Iowa, 129 East Jefferson, Iowa City, IA 52242, USABernd Fritzsch - Department of Biology, University of Iowa, 129 East Jefferson, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Integrative and comparative biology, Vol.58(2), pp.351-365
- DOI
- 10.1093/icb/icy019
- PMID
- 29718413
- PMCID
- PMC6104702
- NLM abbreviation
- Integr Comp Biol
- ISSN
- 1540-7063
- eISSN
- 1557-7023
- Publisher
- Oxford University Press
- Grant note
- DC013655 / ; ; ; ; ; ;
- Language
- English
- Date published
- 08/2018
- Academic Unit
- Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984070787902771
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