Gene expression analysis of forskolin treated basilar papillae identifies microRNA181a as a mediator of proliferation.
BACKGROUND
Auditory hair cells spontaneously regenerate following injury in birds but not mammals. A better understanding of the molecular events underlying hair cell regeneration in birds may allow for identification and eventually manipulation of relevant pathways in mammals to stimulate regeneration and restore hearing in deaf patients.


RESULTS
Gene expression was profiled in forskolin treated (i.e., proliferating) and quiescent control auditory epithelia of post-hatch chicks using an Affymetrix whole-genome chicken array after 24 (n = 6), 48 (n = 6), and 72 (n = 12) hours in culture. In the forskolin-treated epithelia there was significant (p<0.05; >two-fold change) upregulation of many genes thought to be relevant to cell cycle control and inner ear development. Gene set enrichment analysis was performed on the data and identified myriad microRNAs that are likely to be upregulated in the regenerating tissue, including microRNA181a (miR181a), which is known to mediate proliferation in other systems. Functional experiments showed that miR181a overexpression is sufficient to stimulate proliferation within the basilar papilla, as assayed by BrdU incorporation. Further, some of the newly produced cells express the early hair cell marker myosin VI, suggesting that miR181a transfection can result in the production of new hair cells.


CONCLUSIONS
These studies have identified a single microRNA, miR181a, that can cause proliferation in the chicken auditory epithelium with production of new hair cells.
Frucht
Corey S
CS
Medical Scientist Training Program, Yale School of Medicine, New Haven, Connecticut, United States of America.
Uduman
Mohamed
M
Duke
Jamie L
JL
Kleinstein
Steven H
SH
Santos-Sacchi
Joseph
J
Navaratnam
Dhasakumar S
DS
D000818:Animals; D049109:Cell Proliferation; D002645:Chickens; D005576:Colforsin / Q000494:pharmacology*; D020536:Enzyme Activators / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006198:Hair Cells, Auditory / Q000166:cytology / Q000187:drug effects; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D009924:Organ Culture Techniques; D009925:Organ of Corti / Q000166:cytology / Q000187:drug effects; D016133:Polymerase Chain Reaction
D020536:Enzyme Activators; D035683:MicroRNAs; D005576:Colforsin