INVOLVEMENT OF PROGRAMMED CELL-DEATH IN MORPHOGENESIS OF THE VERTEBRATE INNER-EAR

An outstanding challenge in developmental biology is to reveal the mec hanisms underlying the morphogenesis of complex organs. A striking exa mple is the developing inner ear of the vertebrate, which acquires a p recise three-dimensional arrangement of its constituent epithelial cel ls to form three semicircular canals, a central vestibule and a coiled cochlea (in mammals). In generating a semicircular canal, epithelial cells seem to 'disappear' from the center of each canal. This phenomen on has been variously explained as (i) transdifferentiation of epithel ium into mesenchyme, (ii) absorption of cells into the expanding canal or (iii) programmed cell death. In this study, an in situ DNA-end lab eling technique (the TUNEL protocol) was used to map regions of cell d eath during inner ear morphogenesis in the chicken embryo from embryon ic days 3.5-10. Regions of cell death previously identified in vertebr ate ears have been confirmed, including the ventromedial otic vesicle, the base of the endolymphatic duct and the fusion plates of the semic ircular canals. New regions of cell death are also described in and ar ound the sensory organs. Reducing normal death using retrovirus-mediat ed overexpression of human bcl-2 causes abnormalities in ear morphogen esis: hollowing of the center of each canal is either delayed or fails entirely. These data provide new evidence to explain the role of cell death in morphogenesis of the semicircular canals.