title: Developmental profiling of spiral ganglion neurons reveals insights into auditory circuit assembly.
abstract: The sense of hearing depends on the faithful transmission of sound information from the ear to the brain by spiral ganglion (SG) neurons. However, how SG neurons develop the connections and properties that underlie auditory processing is largely unknown. We catalogued gene expression in mouse SG neurons from embryonic day 12, when SG neurons first extend projections, up until postnatal day 15, after the onset of hearing. For comparison, we also analyzed the closely related vestibular ganglion (VG). Gene ontology analysis confirmed enriched expression of genes associated with gene regulation and neurite outgrowth at early stages, with the SG and VG often expressing different members of the same gene family. At later stages, the neurons transcribe more genes related to mature function, and exhibit a dramatic increase in immune gene expression. Comparisons of the two populations revealed enhanced expression of TGFβ pathway components in SG neurons and established new markers that consistently distinguish auditory and vestibular neurons. Unexpectedly, we found that Gata3, a transcription factor commonly associated with auditory development, is also expressed in VG neurons at early stages. We therefore defined new cohorts of transcription factors and axon guidance molecules that are uniquely expressed in SG neurons and may drive auditory-specific aspects of their differentiation and wiring. We show that one of these molecules, the receptor guanylyl cyclase Npr2, is required for bifurcation of the SG central axon. Hence, our dataset provides a useful resource for uncovering the molecular basis of specific auditory circuit assembly events.
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Cindy C
authors.initials: CC
authors.lastname: Lu
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Appler
authors.forename: E Andres
authors.initials: EA
authors.lastname: Houseman
authors.forename: Lisa V
authors.initials: LV
authors.lastname: Goodrich
mesh_terms: D000465:Algorithms; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology; D052004:Bone Morphogenetic Protein Receptors / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D004622:Embryo, Mammalian; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D066298:In Vitro Techniques; D051258:MafB Transcription Factor / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D039781:PubMed / Q000706:statistics & numerical data; D036123:Receptor, EphA5 / Q000235:genetics / Q000378:metabolism; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics; D015203:Reproducibility of Results; D013136:Spiral Ganglion / Q000166:cytology* / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D000099242:Atrial Natriuretic Factor Receptor B
chemical_list: D052004:Bone Morphogenetic Protein Receptors; D050990:GATA3 Transcription Factor; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D051258:MafB Transcription Factor; D036123:Receptor, EphA5; D017461:Receptors, Atrial Natriuretic Factor; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000099242:Atrial Natriuretic Factor Receptor B; C494748:Gata3 protein, mouse; C490406:Mafb protein, mouse; C487377:Tlx3 protein, mouse