CRABP-I Expression Patterns in the Developing Chick Inner Ear

SIMPLE SUMMARY: Retinoic acid is an important signal required for a high number of molecular and cellular processes in embryonic and postnatal development, as well as adult functions. Alterations of retinoic acid levels cause birth defects when it is deficient or in excess. CRABP-I governs the effects of retinoic acid sequestering and regulating its differential accumulation in the cytoplasm. The spatiotemporal expression patterns of CRABP-I in the developing chick inner ear were characterized to better clarify the potential role of CRABP-I in managing the retinoic acid signaling pathway. The heterogeneity of the CRABP-I expression pattern in the developing otic epithelium strongly suggests that CRABP-I may play a role in the specification of the dorsal-to-ventral axis of the otic anlagen, as well as in the specification of each sensory element as development proceeds. CRABP-I may also be involved in the final differentiation of neurons of the developing acoustic-vestibular ganglion that will innervate the sensory patches of this intricate sensory organ. These results suggest the direct involvement of CRABP-I in the epithelial specification and final differentiation of tissue and cells, as well as in morphogenetic events, which take place during embryonic development. ABSTRACT: The vertebrate inner ear is a complex three-dimensional sensorial structure with auditory and vestibular functions, regarded as an excellent system for analyzing events that occur during development, such as patterning, morphogenesis, and cell specification. Retinoic acid (RA) is involved in all these development processes. Cellular retinoic acid-binding proteins (CRABPs) bind RA with high affinity, buffering cellular free RA concentrations and consequently regulating the activation of precise specification programs mediated by particular regulatory genes. In the otic vesicle, strong CRABP-I expression was detected in the otic wall’s dorsomedial aspect, where the endolymphatic apparatus develops, whereas this expression was lower in the ventrolateral aspect, where part of the auditory system forms. Thus, CRABP-I proteins may play a role in the specification of the dorsal-to-ventral and lateral-to-medial axe of the otic anlagen. Regarding the developing sensory patches, a process partly involving the subdivision of a ventromedial pro-sensory domain, the CRABP-I gene displayed different levels of expression in the presumptive territory of each sensory patch, which was maintained throughout development. CRABP-I was also relevant in the acoustic-vestibular ganglion and in the periotic mesenchyme. Therefore, CRABP-I could protect RA-sensitive cells in accordance with its dissimilar concentration in specific areas of the developing chick inner ear.