Abstract
BackgroundThe 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.ResultsHere 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.ConclusionOur 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.
Highlights
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
Our experiments revealed that BMP4 signaling is involved in generation of sensory epithelia by negatively regulating inner ear progenitor cell proliferation through downregulation of the homeodomain transcription factor Pax-2
Exogenous BMP4 leads to increase in hair cell numbers and blockade of bone morphogentic proteins (BMPs) signaling inhibits hair cell generation Maintenance of the developing avian inner ear in vitro in an environment with largely reduced extrinsic influences can be facilitated by removal of periotic mesenchyme, which otherwise could serve as source for various signaling molecules [11,12]
Summary
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. Malformed or missing cristae were observed in these experiments, the hair cells developed normally These results did not clarify why BMP4 is robustly expressed in sensory epithelia primordia thereby neither confirming nor refuting the hypothesis that BMP signaling is involved in the genesis of inner ear sensory organs. A possible explanation for the previously observed lack of sensory epithelia defects after in ovo application of BMP4 antagonists is that the antagonists did not penetrate far enough to reach sufficiently high concentrations in the developing sensory epithelia to block BMP signaling effectively To address this issue, we exploited a serum-free floating otocyst culture system, which allowed us to quantitatively analyze progenitor cell proliferation, apoptosis and cell differentiation in the developing otocyst with loss of function and gain of function experiments.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
