Gene expression analysis of forskolin treated basilar papillae identifies microRNA181a as a mediator of proliferation.

PloS One
Corey S FruchtDhasakumar S Navaratnam

Abstract

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. 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...Continue Reading

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Citations

Jun 30, 2012·EMBO Molecular Medicine·Anya Rudnicki, Karen B Avraham
Mar 15, 2011·Journal of the Association for Research in Otolaryngology : JARO·Corey S FruchtDhasakumar S Navaratnam
Apr 10, 2012·Hearing Research·Minal Patel, Bo Hua Hu
Mar 3, 2012·Hearing Research·Xian-Ren WangHongyan Jiang
Nov 26, 2015·Neuroscience and Biobehavioral Reviews·Juan F Codocedo, Nibaldo C Inestrosa
Feb 15, 2011·Neuroscience Letters·Corey S FruchtDhasakumar S Navaratnam
Jan 15, 2014·Microarrays·Michael E Smith, Gopinath Rajadinakaran
Dec 8, 2017·Yonsei Medical Journal·Chang Woo KimJae Young Choi
Feb 3, 2018·Aging and Disease·Weiming HuJianguo Tang
Feb 12, 2021·Frontiers in Cell and Developmental Biology·Giulia GentileFabio Mammano

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Methods Mentioned

BETA
PCR
transfection
ChIP

Software Mentioned

GeneSpring
Affymetrix
Bioconductor
GENMAPP
GSEAs
TRANSFAC
R
GeneSpring GX
all
GSEA

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