Journal article
Lmx1a and Lmx1b are Redundantly Required for the Development of Multiple Components of the Mammalian Auditory System
Neuroscience, Vol.452, pp.247-264
01/01/2021
DOI: 10.1016/j.neuroscience.2020.11.013
PMCID: PMC7780644
PMID: 33246067
Abstract
•Combined loss of Lmx1a/b disrupts auditory inner ear development, preventing formation of the organ of Corti.•Loss of Lmx1a and Lmx1b leads to milder inner ear vestibular innervation abnormalities.•In Lmx1a/b double mutants, vestibular afferents aberrantly project to the hindbrain dorsal midline.•Combined loss of Lmx1a/b prevents the development of excitatory neurons of cochlear and vestibular nuclei.
The inner ear, projections, and brainstem nuclei are essential components of the auditory and vestibular systems. It is believed that the evolution of complex systems depends on duplicated sets of genes. The contribution of duplicated genes to auditory or vestibular system development, however, is poorly understood. We describe that Lmx1a and Lmx1b, which originate from the invertebrate Lmx1b-like gene, redundantly regulate development of multiple essential components of the mammalian auditory/vestibular systems. Combined, but not individual, loss of Lmx1a/b eliminated the auditory inner ear organ of Corti (OC) and disrupted the spiral ganglion, which was preceded by a diminished expression of their critical regulator Pax2. Innervation of the remaining inner ear vestibular organs revealed unusual sizes or shapes and was more affected compared to Lmx1a/b single-gene mutants. Individual loss of Lmx1a/b genes did not disrupt brainstem auditory nuclei or inner ear central projections. Combined loss of Lmx1a/b, however, eliminated excitatory neurons in cochlear/vestibular nuclei, and also the expression of a master regulator Atoh1 in their progenitors in the lower rhombic lip (RL). Finally, in Lmx1a/b double mutants, vestibular afferents aberrantly projected to the roof plate. This phenotype was associated with altered expression of Wnt3a, a secreted ligand of the Wnt pathway that regulates pathfinding of inner ear projections. Thus, Lmx1a/b are redundantly required for the development of the mammalian inner ear, inner ear central projections, and cochlear/vestibular nuclei.
Details
- Title: Subtitle
- Lmx1a and Lmx1b are Redundantly Required for the Development of Multiple Components of the Mammalian Auditory System
- Creators
- Victor V Chizhikov - Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USAIgor Y Iskusnykh - Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USANikolai Fattakhov - Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USABernd Fritzsch - Department of Biology, University of Iowa, Iowa, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Neuroscience, Vol.452, pp.247-264
- DOI
- 10.1016/j.neuroscience.2020.11.013
- PMID
- 33246067
- PMCID
- PMC7780644
- NLM abbreviation
- Neuroscience
- ISSN
- 0306-4522
- eISSN
- 1873-7544
- Publisher
- Elsevier Ltd
- Grant note
- name: NIH, award: R01 DC005590 and AG060504, R01 NS093009; name: Neuroscience Institute of the UTHSC
- Language
- English
- Date published
- 01/01/2021
- Academic Unit
- Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984070477902771
Metrics
21 Record Views