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Open Access Highly Accessed Research article

BMP4 signaling is involved in the generation of inner ear sensory epithelia

Huawei Li12*, Carleton E Corrales1, Zhengmin Wang2, Yanling Zhao2, Yucheng Wang2, Hong Liu1 and Stefan Heller1*

Author Affiliations

1 Department of Otolaryngology and Program in Neuroscience, Harvard Medical School and Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA

2 Department of Otolaryngology, Central Laboratory of Eye, Ear, Throat and Nose Hospital, Shanghai Medical College of Fudan University, Shanghai, 200031, PR of China

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BMC Developmental Biology 2005, 5:16  doi:10.1186/1471-213X-5-16

Published: 17 August 2005

Abstract

Background

The robust expression of BMP4 in the incipient sensory organs of the inner ear suggests possible roles for this signaling protein during induction and development of auditory and vestibular sensory epithelia. Homozygous BMP4-/- animals die before the inner ear's sensory organs develop, which precludes determining the role of BMP4 in these organs with simple gene knockout experiments.

Results

Here we use a chicken otocyst culture system to perform quantitative studies on the development of inner ear cell types and show that hair cell and supporting cell generation is remarkably reduced when BMP signaling is blocked, either with its antagonist noggin or by using soluble BMP receptors. Conversely, we observed an increase in the number of hair cells when cultured otocysts were treated with exogenous BMP4. BMP4 treatment additionally prompted down-regulation of Pax-2 protein in proliferating sensory epithelial progenitors, leading to reduced progenitor cell proliferation.

Conclusion

Our results implicate BMP4 in two events during chicken inner ear sensory epithelium formation: first, in inducing the switch from proliferative sensory epithelium progenitors to differentiating epithelial cells and secondly, in promoting the differentiation of hair cells within the developing sensory epithelia.