Spatial shaping of cochlear innervation by temporally regulated neurotrophin expression

被引:242
作者
Fariñas, I
Jones, KR
Tessarollo, L
Vigers, AJ
Huang, E
Kirstein, M
de Caprona, DC
Coppola, V
Backus, C
Reichardt, LF
Fritzsch, B [1 ]
机构
[1] Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA
[2] Univ Calif San Francisco, Dept Physiol, Program Neurosci, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
[4] Univ Valencia, Dept Biol Celular, E-46100 Burjassot, Spain
[5] Univ Colorado, Dept Biol, Boulder, CO 80309 USA
[6] Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA
[7] NCI, Neural Dev Grp, Mouse Canc Genet Program, Frederick, MD 21701 USA
基金
英国惠康基金;
关键词
neurotrophins; ear innervation; development of ear innervation; ear and neurotrophin expression; NT-3; sensory neuron survival;
D O I
10.1523/JNEUROSCI.21-16-06170.2001
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Previous work suggested qualitatively different effects of neurotrophin 3 (NT-3) in cochlear innervation patterning in different null mutants. We now show that all NT-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-temporal expression patterns of brain-derived neurotrophic factor (BDNF) and NT-3, using lacZ reporters in each gene and with expression of the specific neurotrophin receptors, trkB and trkC. In the NT-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-temporal gradients of neurotrophin expression. Our immunocytochemical data show equal expression of their receptors, TrkB and TrkC, 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.
引用
收藏
页码:6170 / 6180
页数:11
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