The focus of this project is to identify genes that are important in the normal development of the inner ear using the chick as a model. The inner ear undergoes elaborate morphological changes during development. Perturbation of this developmental process very often leads to functional deficits. A good knowledge of the molecular basis that underlies the morphological events occurring during normal inner ear development will facilitate the understanding of functional deficits resulting from genetic defects. We reported previously that the mRNA encoding for Bone Morphogenetic Protein (BMP) 4, 5 and 7, was present in the developing chick inner ear. Further analysis indicated that BMP4 was an early marker for all sensory organs in the inner ear. However, the distribution of BMP7 mRNA was extensive in the otocyst and included regions of the otic epithelium that were positive for BMP4. As the sensory organs mature, BMP7 mRNA became restricted to the non-sensory portions of the otic epithelium, except in the cochlea where BMP7 messages remained at least until hatching. On the other hand, BMP5 mRNA was found only transiently in the otocyst and may be associated with the presumptive posterior ampulla. These data, taken together with other published results, suggest that the inner ear is molecularly defined at an early stage in development. To test the consequences of disturbing such an intricate gene expression pattern, exogenous retinoic acid was used as a perturbant. Our preliminary results showed tat implantation of retinoic acid-soaked beads into otocysts at embryonic day 2.5 resulted in the malformation of the superior semicircular canal while the gross anatomy of the remaining inner ear remained relatively normal. The mechanism(s) whereby retinoic acid mediates this effect is currently under investigation.
