Addition of the BMP4 antagonist, noggin, disrupts avian inner ear development

Bone morphogenetic protein 4 (BMP4) is known to regulate dorsoventral patte rning, limb bud formation and axis specification in many organisms, includi ng the chicken. In the chick developing inner ear, BMP4 expression becomes localized in two cell clusters at the anterior and posterior edges of the o tic epithelium beginning at stage 16/17 and is expressed in presumptive sen sory tissue at later stages. This restricted spatiotemporal pattern of expr ession occurs just prior to the otocyst's transition to a more complex thre e-dimensional structure. To further analyze the role of BMP4 in avian otic morphogenesis, cells expressing BMP4 or its antagonist, noggin, were grown on agarose beads and implanted into the periotic mesenchyme surrounding the chick otocyst, Although the BMP4-producing cells had no effect on the matu re inner ear structure when implanted alone, noggin-producing cells implant ed adjacent to the BMP4 cell foci prevented normal semicircular canal devel opment. Beads implanted at the anterior BMP4 focus eliminated the anterior and/or the horizontal canals. Noggin cells implanted at the posterior focus eliminated the posterior canal. Canal loss was prevented by coimplantation of BMP4 cell beads nest to noggin beads. An antibody to the chick hair cel l antigen (HCA) was used to examine sensory cell distribution, which was ab normal only in the affected tissues of noggin-exposed inner ears. These dat a suggest a role for BMP4 in the accurate and complete morphological develo pment of the semicircular canals.