Fate specification in mouse inner ear development

Abstract

The embryonic otic epithelium may be viewed as a model system for the study of tissue patterning and cell fate specification in vertebrates. Growth, differentiation, and morphological elaboration transform a simple epithelial cyst into the inner ear labyrinth, along which lie the various mechanosensory organs of balance and hearing. In addition, the otic epithelium is a source of neural progenitors for the VIIIth cranial (vestibulocochlear) sensory ganglion, which innervates the ear. Developmental mechanisms governing the segregation of neural and sensory organ progenitor lineages during inner ear development are currently unknown. A prevailing hypothesis holds that the otocyst is compartmentalized along its major axes by selector gene activity, and that nascent sensory organ territories are induced at compartment boundaries. Otocyst expression of early neural markers is also regionalized, therefore neural- and sensory-competent states may be spatially segregated from the outset of progenitor cell determination. Other lines of evidence suggest the existence of a common neural- and sensory-competent region, in which case these states may be expressed in temporal succession by a multi-potent progenitor cell pool. Either scenario allows for the possibility that sensory organ induction must be accompanied by active neurogenic suppression. I show that the T-box gene Tbx1/TBX1 is necessary and sufficient to suppress otocyst neurogenesis. Furthermore, Tbx1 is required for sensory organ-associated gene expression and proper morphogenesis of inner ear sensory organs. Results obtained are consistent with an involvement of both pro-neural/pro-sensory tissue compartmentalization and common progenitor pool fate switching during otocyst stages of ear development. These different processes are distributed by otocyst position, but both processes are mediated by Tbx1 activity. I hypothesize that all prospective sensory organ territories of the otocyst are either latently or transiently neurogenic.