Correlation of Pax-2 expression with cell proliferation in the developing chicken inner ear.

In vertebrates, the paired-box transcription factor Pax-2 is one of the earliest markers of the developing inner ear and is robustly expressed in the otic placode and the otic vesicle. Mutations in the Pax-2 gene result in developmental defects of the vestibular and auditory apparatus. We set out to investigate whether regions of Pax-2 expression in the developing otic vesicle correlate with areas of cell proliferation or cell death, which would indicate a possible role of Pax-2 in these processes. Regionalized proliferation and local apoptosis are the principal mechanisms that lead to the complex morphogenesis of the highly compartmentalized inner ear starting from a simple vesicle. We found a high correlation of Pax-2 expression with proliferating cells in the walls of the early otic vesicle. Apoptotic cells were mostly localized outside of the Pax-2-expressing regions. At later stages, we found the highest intensity of proliferating and Pax-2-positive cells in areas of the developing sensory epithelia. When hair cells begin to differentiate, they maintain a lower level of Pax-2 expression than neighboring cells for a brief period, before they completely down-regulate expression of this transcription factor. We conclude that a significant proportion of proliferating cells in the developing otocyst express Pax-2, in particular in regions that include developing sensory patches. This implicates Pax-2 as a marker for proliferating hair and supporting cell progenitors. Furthermore, the likelihood that Pax-2-expressing cells in the otocyst die by apoptosis is much lower when compared with cells residing in Pax-2-negative regions. Copyright 2004 Wiley Periodicals, Inc. J Neurobiol 60: 61-70, 2004