NDLI: In vivo Notch Reactivation in Differentiating Cochlear Hair Cells Induces Sox2 and Prox1 Expression but Does Not Disrupt Hair Cell Maturation

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In vivo Notch Reactivation in Differentiating Cochlear Hair Cells Induces Sox2 and Prox1 Expression but Does Not Disrupt Hair Cell Maturation

Content Provider	PubMed Central
Author	Liu, Zhiyong Owen, Thomas Fang, Jie Srinivasan, R. Sathish Zuo, Jian
Abstract	Notch signaling is active in mouse cochlear prosensory progenitors but declines in differentiating sensory hair cells (HCs). Overactivation of the Notch1 intracellular domain (NICD) in progenitors blocks HC fate commitment and/or differentiation. However, it is not known whether reactivation of NICD in differentiating HCs also interrupts their developmental program and reactivates its downstream targets. By analyzing Atoh1CreER+; Rosa26-NICDloxp/+ or Atoh1CreER+; Rosa26-NICDloxp/+; RBP-Jloxp/loxp mice, we demonstrated that ectopic NICD in differentiating HCs caused reactivation of Sox2 and Prox1 in an RBP-J–dependent manner. Interestingly, Prox1 reactivation was exclusive to outer HCs (OHCs). In addition, lineage tracing analysis of Prox1CreER/+; Rosa26-EYFPloxp/+ and Prox1CreEGFP/+; Rosa26-EYFPloxp/+ mice showed that nearly all HCs experiencing Prox1 expression were OHCs. Surprisingly, these HCs still matured normally with expression of prestin, wild-type-like morphology and uptake of FM4-64FX dye at adult ages. Our results suggest that the developmental program of cochlear differentiating HCs is refractory to Notch reactivation and that Notch is an upstream regulator of Sox2 and Prox1 in cochlear development. In addition, our results support that Sox2 and Prox1 should not be the main blockers for terminal differentiation of HCs newly regenerated from postnatal cochlear SCs that still maintain Sox2 and Prox1 expression.
Related Links	http://dx.doi.org/10.1002/dvdy.23754
Ending Page	696
Page Count	13
Starting Page	684
File Format	PDF
ISSN	10588388
e-ISSN	10970177
Journal	Developmental Dynamics
Issue Number	4
Volume Number	241
Language	English
Publisher Date	2012-04-01
Access Restriction	Open
Subject Keyword	Developmental Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Developmental Biology

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In vivo Notch Reactivation in Differentiating Cochlear Hair Cells Induces Sox2 and Prox1 Expression but Does Not Disrupt Hair Cell Maturation

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In vivo Notch Reactivation in Differentiating Cochlear Hair Cells Induces Sox2 and Prox1 Expression but Does Not Disrupt Hair Cell Maturation