RETINOIC ACID DISTURBS MOUSE MIDDLE-EAR DEVELOPMENT IN A STAGE-DEPENDENT FASHION

The mammalian middle ear contains a chain of three ossicles, the malle us, incus, and stapes, that transmit into the inner ear the vibrations produced in the tympanic membrane by aerial sound. I show here that r etinoic acid interferes with the formation of the middle ear in a stag e-specific fashion. The malformations produced are derived from a reti noic acid-induced inhibition of the formation and/or migration of the cranial neural crest that generates the middle ear skeletal elements a nd not from a respecification of neural crest identity to more posteri or fates. I have used these effects of retinoic acid to analyze the te mporal sequence of events involved in the morphogenesis of the middle ear. I show that the middle ear bones develop from several primordia t hat originate in a typical temporal sequence from Day 8 plus 4.5 hr to Day 8 plus 7.5 hr of pregnancy. Moreover, interactions between adjace nt bones are not required for their proper formation. My results also suggest a Hoxa-2-mediated patterning of the otic capsule in the region where the oval window is located. (C) 1997 Academic Press.