Ectopic Noggin blocks sensory and nonsensory organ morphogenesis in the chicken inner ear

Bone morphogenetic protein 4 (Bmp4) is expressed during multiple stages of development of the chicken inner ear. At the otocyst stage, Bmp4 is express ed in each presumptive sensory organ, as well as in the mesenchymal cells s urrounding the region of the otocyst that is destined to form the semicircu lar canals. After the formation of the gross anatomy of the inner ear, Bmp4 expression persists in some sensory organs and restricted domains of the s emicircular canals. To address the role of this gene in inner ear developme nt, we blocked BMP4 function(s) by delivering one of its antagonists, Noggi n, to the developing inner ear in ovo. Exogenous Noggin was delivered to th e developing otocyst by using a replication-competent avian retrovirus enco ding the Noggin cDNA (RCAS-N) or implanting beads coated with Noggin protei n. Noggin treatment resulted in a variety of phenotypes involving both sens ory and nonsensory components of the inner ear. Among the nonsensory struct ures, the semicircular canals were the most sensitive and the endolymphatic duct and sac most resistant to exogenous Noggin. Noggin affected the proli feration of the primordial canal outpouch, as well as the continual outgrow th of the canal after its formation. In addition, Noggin affected the struc tural patterning of the cristae, possibly via a decrease of Msx1 and p75NGF R expression. These results suggest that BMP4 and possibly other BMPs are r equired for multiple phases of inner ear development, (C) 1999 Academic Pre ss.