A Comparative Analysis of Avian and Mammalian Inner Ear Development and Regeneration
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چکیده
Deafness, hearing, and balance disorders are common worldwide. The inner ear sensory hair cells are the mechanoreceptors that detect sound, head motion, and linear acceleration. Loss of or damage to hair cells is the major cause of hearing and balance disorders in humans. Nonmammalian vertebrates (birds, fish, and amphibians) have the ability to regenerate sensory hair cells, whereas mammals can not regenerate damages/lost hair cells. In this study we have analyzed the first large scale gene expression profiles (provided by other members of the Lovett lab) of avian and mammalian (mouse) inner ear development and regeneration to further understand and identify signaling pathways that regulate hair cell regeneration. We have compared the avian hair cell regenerative program to the normal mammalian developmental program by: (i) constructing self-organizing maps (SOMs) and comparing these across the two species in the relevant tissues, and (ii) generating possible functional pathways and networks using Ingenuity Pathways Analysis. There were 177 differentially expressed genes that are cochlea-specific; among which we found EGR1, EP300, ESR1, and FOG2. Another comparison revealed 66 differentially expressed utricle-specific genes, which contained CEBPG, ESR1, JUN, and TGFB1|1. A Comparison between chicken cochlea and mouse developmental dataset revealed 18 genes (e.g., FOS, HEYL, NEUROD1) that are common between the two profiles. Another comparison was conducted between the chicken utricle profile and the mouse developmental profile, which revealed 8 genes (e.g, HEY1, ID1) in common. On the other hand, Self Organizing Maps (SOMs) were generated for cochlea-specific, utricle-specific, and mouse developmental profiles to cluster genes with similar expression patterns. Through the use of Ingenuity Pathways Analysis (IPA) application we were able to identify possible networks and functional pathways that are activated during avian hair cell regeneration and mammalian hair cell development.
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تاریخ انتشار 2008