THE DEVELOPMENT OF THE VERTEBRATE INNER-EAR

The inner ear is a complex sensory organ responsible for balance and s ound detection in vertebrates. It originates from a transient embryoni c structure, the otic vesicle, that contains all of the information to develop autonomously into the mature inner ear. We review here the de velopment of the otic vesicle, bringing together classical embryologic al experiments and recent genetic and molecular data. The specificatio n of the prospective ectoderm and its commitment to the otic fate are very early events and can be related to the expression of genes with r estricted expression domains. A combinatorial gene expression model fo r placode specification and diversification, based on classical embryo logical evidence and gene expression patterns, is discussed. The forma tion of the otic vesicle is dependent on inducing signals from endoder m, mesoderm and neuroectoderm. Ear induction consists of a sequence of discrete instructions from those tissues that confer its final identi ty on the otic field, rather than a single all-or-none process. The im portant role of the neural tube in otic development is highlighted by the abnormalities observed in mouse mutants for the Hoxa1, kreisler an d fgf3 genes and those reported in retinoic acid-deficient quails. Sti ll, the nature of the relation between the neural tube and otic develo pment remains unclear. Gene targeting experiments in the mouse have pr ovided evidence for genes potentially involved in regional and cell-fa te specification in the inner ear. The disruption of the mouse Brn3.1 gene identifies the first mutation affecting sensory hair-cell specifi cation, and mutants for Pax2 and Nkx5.1 genes show their requirement f or the development of specific regions of the otic vesicle. Several gr owth-factors contribute to the patterned cell proliferation of the oti c vesicle. Among these, IGF-I and FGF-2 are expressed in the otic vesi cle and may act in an autocrine manner. Finally, little is known about early mechanisms involved in guiding ear innervation. However, target ed disruption of genes coding for neurotrophins and Trk receptors have shown that once synaptic contacts are established, they depend on spe cific trophic interactions that involve these two gene families. The a ccessibility of new cellular and molecular approaches are opening new perspectives in vertebrate development and are also starting to be app lied to ear development. This will allow this classical and attractive model system to see a rapid progress in the near future. (C) 1998 Els evier Science Ireland Ltd.