MicroRNA181a mediates chicken auditory hair cell regeneration

Auditory hair cells, the mechanosensitive cells that respond to acoustic stimulation and underlie the sense of hearing, regenerate after injury in non-mammalian vertebrates such as birds and fish but not in mammals. The regenerative response in the bird inner ear has been well characterized and is known to be rapid, extensive, and result in functional recovery. Given that microRNAs (miRNA) are capable of down-regulating in a coordinated fashion networks of genes that may be functionally linked, many have postulated that they may be important for hair cell regeneration, a process in which cells are rapidly changing their program and going from a state of perpetual quiescence when stimulated to divide and differentiate in response to a stimulus such as injury. To gain insight into the molecular events underlying this phenomenon gene expression profiles were compared between proliferating and quiescent chicken auditory epithelia, also known as basilar papillae (BP). Computational analysis predicted activation of multiple miRNAs in the proliferating tissue; the most significant of these was microRNA181a. This miRNA was selected for functional validation given that it is known to have an important proliferative role in other systems.

BPs transfected with miR181a in-vitro had significantly more proliferation than BPs transfected with a non-targeting miRNA. Further, some of these newly divided cells began to differentiate into new hair cells. Further work will be required to establish whether these cells mature into fully functional hair cells. Regardless, endogenous miR181a also seems to be important for hair cell regeneration after injury, as knocking down this miRNA causes a marked decrease in the amount of post-injury (i.e., regenerative) proliferation. This single miRNA can therefore stimulate proliferation with production of some new hair cells, and seems to play a key role hair cell regeneration after injury. That this individual miRNA can have such a robust functional effect raises hopes that it and perhaps others may be of some therapeutic benefit for individuals with sensorineural hearing loss.

Frucht et al. Gene Expression Analysis of Forskolin Treated Basilar Papillae Identifies MicroRNA181a as a Mediator of Proliferation. PLoS ONE (2010) vol. 5 (7) pp. e11502

Frucht et al. MicroRNA181a plays a key role in hair cell regeneration in the avian auditory epithelium. Neuroscience Letters (2011) pp. 1-5

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