Gene expression differences in quiescent versus regenerating hair cells of avian sensory epithelia: implications for human hearing and balance disorders.

摘要

The sensory receptors for hearing and balance are the hair cells of the cochlea and vestibular organs of the inner ear. Permanent hearing and balance deficits can be triggered by genetic susceptibilities or environmental factors such as infection. Unlike mammalian hair cells that have a limited capacity for regeneration, the vestibular organ of the avian ear is constantly undergoing hair cell regeneration, whereas the avian cochlea undergoes regeneration only when hair cells are damaged. In order to gain insights into the genetic programs that govern the regenerative capacity of hair cells, we interrogated custom human cDNA microarrays with sensory epithelial cell targets from avian inner ears. The arrays contained probes from conserved regions of approximately 400 genes expressed primarily in the inner ear and approximately 1500 transcription factors (TF). Highly significant differences were observed for 20 inner-ear genes and more than 80 TFs. Genes up-regulated in the cochlea included BMP4, GATA3, GSN, FOXF1 and PRDM7. Genes up-regulated in the utricle included SMAD2, KIT, beta-AMYLOID, LOC51637, HMG20B and CRIP2. Many of the highly significant changes were validated by Q-PCR and in situ methods. Some of the observed changes implicated a number of known biochemical pathways including the c-kit pathway previously observed in melanogenesis. Twenty differentially expressed TFs map to chromosomal regions harboring uncloned human deafness loci, and represent novel candidates for hearing loss. The approach described here also illustrates the power of utilizing conserved human cDNA probes for cross-species comparisons.