Transient, afferent input-dependent, postnatal niche for neural progenitor cells in the cochlear nucleus.
In the cochlear nucleus (CN), the first central relay of the auditory pathway, the survival of neurons during the first weeks after birth depends on afferent innervation from the cochlea. Although input-dependent neuron survival has been extensively studied in the CN, neurogenesis has not been evaluated as a possible mechanism of postnatal plasticity. Here we show that new neurons are born in the CN during the critical period of postnatal plasticity. Coincidently, we found a population of neural progenitor cells that are controlled by a complex interplay of Wnt, Notch, and TGFβ/BMP signaling, in which low levels of TGFβ/BMP signaling are permissive for progenitor proliferation that is promoted by Wnt and Notch activation. We further show that cells with activated Wnt signaling reside in the CN and that these cells have high propensity for neurosphere formation. Cochlear ablation resulted in diminishment of progenitors and Wnt/β-catenin-active cells, suggesting that the neonatal CN maintains an afferent innervation-dependent population of progenitor cells that display active canonical Wnt signaling.
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Stefan
S
Volkenstein
Kazuo
K
Oshima
Saku T
ST
Sinkkonen
C Eduardo
CE
Corrales
Sam P
SP
Most
Renjie
R
Chai
Taha A
TA
Jan
Renée
R
van Amerongen
Alan G
AG
Cheng
Stefan
S
Heller
D000818:Animals; D049109:Cell Proliferation; D017626:Cochlear Nucleus / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D055495:Neurogenesis