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

Title:
Brn3a is a transcriptional regulator of soma size, target field innervation and axon pathfinding of inner ear sensory neurons
Authors:
Huang, Eric J.; Liu, Wei; Fritzsch, Bernd; Bianchi, Lynne M.; Reichardt, Louis F.; Xiang, Mengqing
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-stato-acoustic 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.
Citation:
Huang, E.J., W. Liu, B. Fritzsch, L.M. Bianchi, L.F. Reichardt, and M. Xiang. 2001. "Brn3a is a transcriptional regulator of soma size, target field innervation and axon pathfinding of inner ear sensory neurons." Development 128: 2421-2432.
Publisher:
Company of Biologists
DATE ISSUED:
2001-07-01
Department:
Neuroscience
Type:
article
Additional Links:
http://dev.biologists.org/content/128/13/2421.abstract
PERMANENT LINK:
http://hdl.handle.net/11282/309741

Full metadata record

DC FieldValue Language
dc.contributor.authorHuang, Eric J.en_US
dc.contributor.authorLiu, Weien_US
dc.contributor.authorFritzsch, Bernden_US
dc.contributor.authorBianchi, Lynne M.en_US
dc.contributor.authorReichardt, Louis F.en_US
dc.contributor.authorXiang, Mengqingen_US
dc.date.accessioned2013-12-23T16:16:51Zen
dc.date.available2013-12-23T16:16:51Zen
dc.date.issued2001-07-01en
dc.identifier.citationHuang, E.J., W. Liu, B. Fritzsch, L.M. Bianchi, L.F. Reichardt, and M. Xiang. 2001. "Brn3a is a transcriptional regulator of soma size, target field innervation and axon pathfinding of inner ear sensory neurons." Development 128: 2421-2432.en_US
dc.identifier.issn0950-1991en_US
dc.identifier.urihttp://hdl.handle.net/11282/309741en
dc.description.abstractThe 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-stato-acoustic 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.en_US
dc.language.isoen_USen_US
dc.publisherCompany of Biologistsen_US
dc.relation.urlhttp://dev.biologists.org/content/128/13/2421.abstracten_GB
dc.subject.departmentNeuroscienceen_US
dc.titleBrn3a is a transcriptional regulator of soma size, target field innervation and axon pathfinding of inner ear sensory neuronsen_US
dc.typearticleen_US
dc.identifier.journalDevelopmenten_US
dc.subject.keywordBrn3aen_US
dc.subject.keywordPOU domainen_US
dc.subject.keywordTranscription factoren_US
dc.subject.keywordSpiral ganglionen_US
dc.subject.keywordSpiral ganglionen_US
dc.subject.keywordVestibular ganglionen_US
dc.subject.keywordInnervationen_US
dc.subject.keywordAxon pathfindingen_US
dc.subject.keywordMouseen_US
dc.identifier.volume128en_US
dc.identifier.startpage2421en_US
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