POTENTIAL ROLE OF BFGF AND RETINOIC ACID IN THE REGENERATION OF CHICKEN COCHLEAR HAIR-CELLS

Messenger RNAs (mRNA) of several growth factor receptors and related g enes were examined with reverse transcriptase polymerase chain reactio n (RT-PCR) in normal and noise-damaged chicken basilar papillae (BP). Analysis of the amplification products indicated the presence of mRNAs for epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), insulin-like growth factor receptor (IGFR), insulin receptor (IR), retinoic acid receptor beta (RAR beta), retinoic acid r eceptor gamma (RXR gamma), and basic fibroblast growth factor (BFGF) i n both normal and noise-damaged BP. The RT-PCR products generated were characterized by size and sequencing analysis to confirm the identiti es of the target molecules. The subcellular localization of the mature protein analogs for EGFR, FGFR, IGFR, RAR beta, and BFGF were identif ied using fluorescence immunocytochemistry and confocal laser scanning microscopy. These experiments indicated that EGFR is present in the s tereociliary bundles in the hair cells, IGFR is not present in the cel ls of the BP, BFGF localizes in the nuclei of supporting cells in the BP, but not hair cells or hyaline cells, and that RAR beta localizes i n the perinuclear regions of hair cells. The subcellular distributions of these proteins were consistent in both noise-damaged and control B P. FGFR, in contrast, changed its distribution in the tissue after noi se damage. In normal BP, FGFR is concentrated in the stereocilia of ha ir cells. However, in damaged regions of noise-exposed chick cochleae, FGFR is heavily expressed in the expanded apical regions of the suppo rting cells. These findings suggest that BFGF and retinoic acid may po tentially play a role in the mechanisms which regulate the regeneratio n of chicken cochlear hair cells.