Retinoic acid disturbs mouse middle ear development in a stage-dependent fashion.
The mammalian middle ear contains a chain of three ossicles, the malleus, incus, and stapes, that transmit into the inner ear the vibrations produced in the tympanic membrane by aerial sound. I show here that retinoic acid interferes with the formation of the middle ear in a stage-specific fashion. The malformations produced are derived from a retinoic acid-induced inhibition of the formation and/or migration of the cranial neural crest that generates the middle ear skeletal elements and not from a respecification of neural crest identity to more posterior fates. I have used these effects of retinoic acid to analyze the temporal sequence of events involved in the morphogenesis of the middle ear. I show that the middle ear bones develop from several primordia that 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 adjacent 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.
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Max-Planck Institute of Immunobiology, Freiburg, Germany.
D000818:Animals; D004432:Ear, Middle / Q000187:drug effects / Q000196:embryology* / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009024:Morphogenesis / Q000187:drug effects; D009432:Neural Crest / Q000187:drug effects; D010641:Phenotype; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*
D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C082927:retinoic acid binding protein I, cellular; D014212:Tretinoin