Article

Journal of the Association for Research in Otolaryngology

, Volume 12, Issue 4, pp 423-435

First online:

Gene Expression Gradients along the Tonotopic Axis of the Chicken Auditory Epithelium

  • Corey S. FruchtAffiliated withMedical Scientist Training Program, Yale School of MedicineInterdepartmental Neuroscience Program, Yale University
  • , Mohamed UdumanAffiliated withInterdepartmental Program in Computation Biology and Bioinformatics, Yale UniversityDepartment of Pathology, Yale School of Medicine
  • , Steven H. KleinsteinAffiliated withInterdepartmental Program in Computation Biology and Bioinformatics, Yale UniversityDepartment of Pathology, Yale School of Medicine
  • , Joseph Santos-SacchiAffiliated withDivision of Otolaryngology, Department of Surgery, Yale School of MedicineDepartment of Cellular and Molecular Physiology, Yale School of Medicine
  • , Dhasakumar S. NavaratnamAffiliated withDepartment of Neurobiology, Yale School of MedicineDepartment of Neurology, Yale School of Medicine Email author 

Abstract

There are known differences in the properties of hair cells along the tonotopic axis of the avian auditory epithelium, the basilar papilla (BP). To determine the genetic basis of these differences, we compared gene expression between the high- (HF), middle-, and low-frequency (LF) thirds of 0-day-old chick auditory epithelia. RNA amplified from each sample was hybridized to whole-genome chicken arrays and GeneSpring software was used to identify differentially expressed genes. Two thousand six hundred sixty-three genes were found to be differentially expressed between the HF and LF segments, using a fold-change cutoff of 2 and a p value of 0.05. Many ion channel genes were differentially expressed between the HF and LF regions of the BP, an expression pattern that was previously established for some but not all of these genes. Quantitative PCR was used to verify tonotopic expression of 15 genes, including KCNMA1 (Slo) and its alternatively spliced STREX exon. Gene set enrichment analyses (GSEA) were performed on the microarray data and revealed many microRNA gene sets significantly enriched in the HF relative to the LF end, suggesting a tonotopic activity gradient. GSEA also suggested differential activity of the kinases protein kinase C and protein kinase A at the HF and LF ends, an interesting corollary to the observation that there is tonotopic expression of the STREX exon that confers on Slo sensitivity to the activity of kinases. Taken together, these results suggest mechanisms of induction and maintenance of tonotopicity and enhance our understanding of the complex nature of proximal–distal gene expression gradients in the chicken BP.

Keywords

cochlea development stem cells kinases