The Roles of Retinoic Acid during Inner Ear Development

Abstract The pleiotropic functions of retinoic acid (RA), a diffusible signaling molecule that acts at various stages during vertebrate embryogenesis and morphogenesis, have been studied extensively. The embryopathy generated by RA excess or deficiency affects several organs, including the inner ear. During the first stages of inner ear embryogenesis, RA may be indirectly involved in the induction of the otic placode, a process that appears to be due to complex mechanisms. RA is also implicated in several processes during inner ear ontogenesis, such as the mesenchyme–otic epithelium interactions that lead to otic capsule formation. Since RA synthesizing and metabolizing enzymes, along with RA receptors, are differentially expressed during early inner ear morphogenesis, a direct involvement of RA (especially in the morphogenesis of the labyrinthic epithelia) appears likely. However, current models also favor some indirect actions due to downstream gene regulation within the hindbrain. Later, RA is likely to intervene in the control of cell proliferation and differentiation, thus regulating hair cell differentiation from progenitor cells in the cochlea. The presence of retinoid receptors, along with RA metabolic enzymes, in the inner ear at the time of birth and during postnatal life suggests that the functional involvement of this signaling molecule goes beyond fetal development.