Molecular genetics of pattern formation in the inner ear: Do compartment boundaries play a role?

The membranous labyrinth of the inner ear establishes a precise geometrical topology so that it may subserve the functions of hearing and balance. How this geometry arises from a simple ectodermal placode is under active inve stigation. The placode invaginates to form the otic cup, which deepens befo re pinching off to form the otic vesicle. By the vesicle stage many genes e xpressed in the developing ear have assumed broad, asymmetrical expression domains. We have been exploring the possibility that these domains may refl ect developmental compartments that are instrumental in specifying the loca tion and identity of different parts of the ear. The boundaries between com partments are proposed to be the site of inductive interactions required fo r this specification. Our work has shown that sensory organs and the endoly mphatic duct each arise near the boundaries of broader gene:expression doma ins, lending support to this idea. A further prediction of the model, that the compartment boundaries will also represent lineage-restriction compartm ents, is supported in part by fate mapping the otic cup. Our data suggest t hat two lineage-restriction boundaries intersect at the dorsal pole of the otocyst, a convergence that may be critical for the specification of endoly mphatic duct outgrowth. We speculate that the patterning information necess ary to establish these two orthogonal boundaries may emanate, in part, from the hindbrain. The compartment boundary model of ear development now needs to be tested through a variety of experimental perturbations, such as the removal of boundaries, the generation of ectopic boundaries, and/or changes in compartment identity.