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


CONCLUSIONS
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.
Li
Huawei
H
Department of Otolaryngology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA. hwli@shmu.edu.cn
Corrales
Carleton E
CE
Wang
Zhengmin
Z
Zhao
Yanling
Y
Wang
Yucheng
Y
Liu
Hong
H
Heller
Stefan
S
D000818:Animals; D030801:Animals, Genetically Modified; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002645:Chickens; D007758:Ear, Inner / Q000166:cytology*; D004848:Epithelium; D006198:Hair Cells, Auditory / Q000166:cytology; D015398:Signal Transduction / Q000502:physiology*
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins