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Dev Biol. 2011 May 15;353(2):367-79. doi: 10.1016/j.ydbio.2011.03.016. Epub 2011 Mar 21.

Rbpj regulates development of prosensory cells in the mammalian inner ear.

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  • 1Laboratory of Cochlear Development, National Institute on Deafness and other Communication Disorders, National Institutes of Health, NIDCD, NIH, Bethesda, MD 20892, USA. yamamoto@ent.kuhp.kyoto-u.ac.jp

Abstract

The vertebrate inner ear contains multiple sensory patches comprised of hair cells and supporting cells. During development these sensory patches arise from prosensory cells that are specified and maintained through the expression of specific molecular factors. Disruption of Jagged1-mediated notch signaling causes a loss of some sensory patches and disruptions in others, indicating a role in some aspect of prosensory development. However, the presence of some sensory patches suggests that some level of notch activity persists in the absence of Jagged1. Therefore, the transcription factor Rbpj, which is required for nearly all notch function, was deleted in the developing otocyst. Results indicate a nearly complete absence of all prosensory patches in the inner ear with remaining hair cells located predominantly in the extreme apex of the cochlea. However, early markers of prosensory cells are still present in Rbpj-mutants, suggesting that maintenance, rather than induction, of prosensory development is dependent on notch signaling. Moreover, analysis of developing cochleae in Rbpj-mutants indicates changes in the spatiotemporal patterns of expression for p27(kip1), Atoh1 and hair cell differentiation markers implicating notch signaling in the regulation of the timing of cellular differentiation and/or in the maintenance of a stem/progenitor cell stage. Finally, the absence of Rbpj caused increased cell death in the cochlea beginning at E12. These results suggest important roles for Rbpj and notch signaling in multiple aspects of inner ear development including prosensory cell maturation, cellular differentiation and survival.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
21420948
[PubMed - indexed for MEDLINE]
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