@article {Fari{\~n}as6170, author = {Isabel Fari{\~n}as and Kevin R. Jones and Lino Tessarollo and Allison J. Vigers and Eric Huang and Martina Kirstein and Dominique C. de Caprona and Vincenzo Coppola and Carey Backus and Louis F. Reichardt and Bernd Fritzsch}, title = {Spatial Shaping of Cochlear Innervation by Temporally Regulated Neurotrophin Expression}, volume = {21}, number = {16}, pages = {6170--6180}, year = {2001}, doi = {10.1523/JNEUROSCI.21-16-06170.2001}, publisher = {Society for Neuroscience}, abstract = {Previous work suggested qualitatively different effects of neurotrophin 3 (NT-3) in cochlear innervation patterning in different null mutants. We now show that allNT-3 null mutants have a similar phenotype and lose all neurons in the basal turn of the cochlea. To understand these longitudinal deficits in neurotrophin mutants, we have compared the development of the deficit in the NT-3 mutant to the spatial{\textendash}temporal expression patterns of brain-derived neurotrophic factor (BDNF) and NT-3, usinglacZ reporters in each gene and with expression of the specific neurotrophin receptors, trkB and trkC. In theNT-3 mutant, almost normal numbers of spiral ganglion neurons form, but fiber outgrowth to the basal turn is eliminated by embryonic day (E) 13.5. Most neurons are lost between E13.5 and E15.5. During the period preceding apoptosis, NT-3 is expressed in supporting cells, whereas BDNF is expressed mainly in hair cells, which become postmitotic in an apical to basal temporal gradient. During the period of neuronal loss, BDNF is absent from the basal cochlea, accounting for the complete loss of basal turn neurons in the NT-3 mutant. The spatial gradients of neuronal loss in these two mutants appear attributable to spatial{\textendash}temporal gradients of neurotrophin expression. Our immunocytochemical data show equal expression of their receptors, TrkB andTrkC, in spiral sensory neurons and thus do not relate to the basal turn loss. Mice in which NT-3 was replaced by BDNF show a qualitative normal pattern of innervation at E13.5. This suggests that the pattern of expression of neurotrophins rather than their receptors is essential for the spatial loss of spiral sensory neurons in NT-3 null mutants.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/21/16/6170}, eprint = {https://www.jneurosci.org/content/21/16/6170.full.pdf}, journal = {Journal of Neuroscience} }