Brn3a is a transcriptional regulator of soma size, target field innervation and axon pathfinding of inner ear sensory neurons

Eric J Huang; Wei Liu; Bernd Fritzsch; Lynne M Bianchi; Louis F Reichardt; Mengqing Xiang

doi:10.1242/dev.128.13.2421

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Brn3a is a transcriptional regulator of soma size, target field innervation and axon pathfinding of inner ear sensory neurons

Journal article

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Brn3a is a transcriptional regulator of soma size, target field innervation and axon pathfinding of inner ear sensory neurons

Eric J Huang, Wei Liu, Bernd Fritzsch, Lynne M Bianchi, Louis F Reichardt and Mengqing Xiang

Development (Cambridge), Vol.128(13), pp.2421-2432

07/2001

DOI: 10.1242/dev.128.13.2421

PMCID: PMC2710107

PMID: 11493560

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Abstract

The POU domain transcription factors Brn3a, Brn3b and Brn3c are required for the proper development of sensory ganglia, retinal ganglion cells, and inner ear hair cells, respectively. We have investigated the roles of Brn3a in neuronal differentiation and target innervation in the facial-statoacoustic ganglion. We show that absence of Brn3a results in a substantial reduction in neuronal size, abnormal neuronal migration and downregulation of gene expression, including that of the neurotrophin receptor TrkC, parvalbumin and Brn3b. Selective loss of TrkC neurons in the spiral ganglion of Brn3a −/− cochlea leads to an innervation defect similar to that of TrkC −/− mice. Most remarkably, our results uncover a novel role for Brn3a in regulating axon pathfinding and target field innervation by spiral and vestibular ganglion neurons. Loss of Brn3a results in severe retardation in development of the axon projections to the cochlea and the posterior vertical canal as early as E13.5. In addition, efferent axons that use the afferent fibers as a scaffold during pathfinding also show severe misrouting. Interestingly, despite the well-established roles of ephrins and EphB receptors in axon pathfinding, expression of these molecules does not appear to be affected in Brn3a −/− mice. Thus, Brn3a must control additional downstream genes that are required for axon pathfinding.

Vestibular ganglion

Spiral ganglion

Mouse

Innervation

Axon pathfinding

Brn3a

Transcription factor

POU domain

Details

Title: Subtitle: Brn3a is a transcriptional regulator of soma size, target field innervation and axon pathfinding of inner ear sensory neurons
Creators: Eric J Huang - Program in Neuroscience, Department of Physiology, and Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA
Wei Liu - Rutgers, The State University of New Jersey
Bernd Fritzsch - University of Iowa, Biology
Lynne M Bianchi - Neuroscience Program, Oberlin College, Oberlin, OH, USA
Louis F Reichardt - Program in Neuroscience, Department of Physiology, and Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA
Mengqing Xiang - Graduate Program in Molecular Genetics and Microbiology, Center for Advanced Biotechnology and Medicine, and Department of Pediatrics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA
Resource Type: Journal article
Publication Details: Development (Cambridge), Vol.128(13), pp.2421-2432
DOI: 10.1242/dev.128.13.2421
PMID: 11493560
PMCID: PMC2710107
NLM abbreviation: Development
ISSN: 0950-1991
eISSN: 1477-9129
Language: English
Date published: 07/2001
Academic Unit: Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
Record Identifier: 9984071780702771

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