THE DEVELOPING ORGAN OF CORTI CONTAINS RETINOIC ACID AND FORMS SUPERNUMERARY HAIR-CELLS IN RESPONSE TO EXOGENOUS RETINOIC ACID IN CULTURE

The mammalian organ of Corti has one of the most highly ordered patter ns of cells in any vertebrate sensory epithelium. A single row of inne r hair cells and three or four rows of outer hair cells extend along i ts length. The factors that regulate the formation of this strict patt ern are unknown. In order to determine whether retinoic acid plays a r ole during the development of the organ of Corti, exogenous retinoic a cid was added to embryonic mouse cochleae in vitro. Exogenous retinoic acid significantly increased the number of cells that developed as ha ir cells and resulted in large regions of supernumerary hair cells and supporting cells containing two rows of inner hair cells and up to 11 rows of outer hair cells. The effects of retinoic acid were dependent on concentration and on the timing of its addition. Western blot anal ysis indicated that cellular retinoic acid binding protein (CRABP) was present in the sensory epithelium of the embryonic cochlea. The amoun t of CRABP apparently increased between embryonic day 14 and postnatal day 1, but CRABP was not detectable in sensory epithelia from adults. A retinoic acid reporter cell line was used to demonstrate that retin oic acid was also present in the developing organ of Corti between emb ryonic day 14 and postnatal day 1, and was also present in adult cochl eae at least in the vicinity of the modiolus. These results suggest th at retinoic acid is involved in the normal development of the organ of Corti and that the effect of retinoic acid may be to induce a populat ion of prosensory cells to become competent to differentiate as hair c ells and supporting cells.