Coupling adhesion to actin bundles in the inner ear. Novel functions for novel cadherins.

Abstract

Genotype and phenotype define two poles of modern biology. The great challenge is to understand the connections that translate gene products into tissue architecture and function. Two recent studies (Boeda et al ., 2002; Siemens et al ., 2002) exemplify how these connections can be identified during the development of the inner ear. The sensory hair cells of the inner ear detect sound and postural change by sensing movement in the endolymph fluid of the cochlea and the semicircular canals, respectively. At the subcellular level, mechano‐sensing is mediated by organelles called stereocilia (SC)—fine, finger‐like protrusions that project from the apices of the hair cells. The morphology and organization of SC are strikingly precise: in mature hair cells, SC increase regularly in height from one side of the cell to the other and are attached to one another by several lateral connections, thereby integrating individual SC into functional units. Developmental mechanisms must therefore exist to coordinate the growth and lateral interactions between SC. The importance of SC morphogenesis becomes apparent in Usher syndrome type 1. Mouse models of this disease show deafness and vestibular dysfunction and have SC that grow haphazardly and lose lateral interactions with one another. Seven genetic loci are independently able to cause this syndrome when mutated (reviewed in Petit, 2001). The corresponding genes for four of these loci encode the unconventional motor protein myosin VIIa, the cytoplasmic protein harmonin, and two transmembrane proteins of the cadherin superfamily, cadherin 23 (CDH23) and protocadherin 15. How these apparently diverse gene products generate …