Cell proliferation and cell death in the developing chick inner ear: spatial and temporal patterns

Morphogenesis of the inner ear is a complex process in which the balance of cell division and death is presumed to play an important role. Surprisingly, there are no reports of a systematic comparison of these two processes in individual ears at different stages of development. This study presents such an analysis for the chicken otocyst at stages 13-29 (embryonic days 2.5-6). To detect proliferating cells, we used exposure to bromodeoxyuridine. To detect apoptotic cells, we used nuclear condensation and fragmentation or terminal dUTP nick-end labeling (TUNEL). The spatial and temporal locations of proliferating and dying cells were mapped across serial sections, revealing regional differences in proliferation within the otocyst epithelium that are more complex than previously reported. In addition, almost all of the previously identified "hot spots" of cell death correspond spatially to regions of reduced cell proliferation. An exception is the ventromedial hot spot of cell death, which is intermingled with proliferating cells when it first appears at stages 19-23 before becoming a cold spot of proliferation. The results further show that the inferior part of the otocyst has a high level of proliferation, whereas the superior part does not. Since the superior part of the otocyst demonstrates outward expansion that is comparable to the inferior part, it appears that regional outgrowth of the otic vesicle is not necessarily coupled to cell proliferation. This study provides a basis for exploring the regulation and function of cell proliferation and cell death during inner ear morphogenesis.