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Updated: Feb 26, 2026
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Published on: June 16, 2022
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Auditory cortex interneuron development requires cadherins operating hair-cell mechanoelectrical transduction
Baptiste Libé-Philippot1,2,3, Vincent Michel1,2,3, Jacques Boutet de Monvel1,2,3
1Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, 75015 Paris, France.
Summary
Congenital deafness may involve intrinsic auditory cortex deficits. Cadherin-related proteins (cdhr23, cdhr15) are crucial for interneuron migration to the auditory cortex, impacting its development and function.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Congenital deafness often results from cochlear hair bundle defects, impacting auditory cortex (AC) maturation.
- The potential for intrinsic AC deficits alongside cochlear issues remains largely unexplored.
- GABAergic interneurons play a critical role in cortical development and function.
Purpose of the Study:
- To investigate whether specific proteins involved in cochlear hair bundles are also expressed by developing interneurons.
- To determine the role of cadherin-related (cdhr) proteins (cdhr23, cdhr15) in interneuron migration and AC development.
- To explore the implications of these findings for understanding congenital deafness and developing therapeutic strategies.
Main Methods:
- Analysis of cdhr23 and cdhr15 expression in GABAergic interneurons during development.
- Generation and analysis of mutant mice lacking cdhr23 or cdhr15.
- In vitro studies to assess cell polarity and migration.
- Investigation of the role of adhesion G protein-coupled receptor V1 (adgrv1).
Main Results:
- Mutant mice lacking cdhr23 or cdhr15 showed a significant reduction in AC parvalbumin interneurons and audiogenic seizures.
- Interneuron precursors expressing cdhr23/cdhr15 exhibited migration defects in cdhr23-/- and cdhr15-/- embryos.
- Impaired cortical entry of interneuron precursors was also observed in the absence of adgrv1.
Conclusions:
- Specific cadherin-related proteins (cdhr23, cdhr15) are essential for the migration of a subset of interneurons to the developing auditory cortex.
- These findings reveal an 'early adhesion code' that guides interneuron precursors to specific neocortical regions.
- This research opens new avenues for auditory rehabilitation and therapeutic interventions for cortical dysfunction in patients.
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