WDR1 colocalizes with ADF and actin in the normal and noise-damaged chick cochlea.
Auditory hair cells of birds, unlike hair cells in the mammalian organ of Corti, can regenerate following sound-induced loss. We have identified several genes that are upregulated following such an insult. One gene, WDR1, encodes the vertebrate homologue of actin-interacting protein 1, which interacts with actin depolymerization factor (ADF) to enhance the rate of actin filament cleavage. We examined WDR1 expression in the developing, mature, and noise-damaged chick cochlea by in situ hybridization and immunocytochemistry. In the mature cochlea, WDR1 mRNA was detected in hair cells, homogene cells, and cuboidal cells, all of which contain high levels of F-actin. In the developing inner ear, WDR1 mRNA was detected in homogene cells and cuboidal cells by embryonic day 7, in the undifferentiated sensory epithelium by day 9, and in hair cells at embryonic day 16. We also demonstrated colocalization of WDR1, ADF, and F-actin in all three cell types in the normal and noise-damaged cochlea. Immediately after acoustic overstimulation, WDR1 mRNA was seen in supporting cells. These cells contribute to the structural integrity of the basilar papilla, the maintenance of the ionic barrier at the reticular lamina, and the generation of new hair cells. These results indicate that one of the immediate responses of the supporting cell after noise exposure is to induce WDR1 gene expression and thus to increase the rate of actin filament turnover. These results suggest that WDR1 may play a role either in restoring cytoskeletal integrity in supporting cells or in a cell signaling pathway required for regeneration.
Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, The University of Michigan Medical School, Ann Arbor, MI 48109-0506, USA.
Seung-Ha
SH
Oh
Henry J
HJ
Adler
Yehoash
Y
Raphael
Margaret I
MI
Lomax
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002642:Chick Embryo / Q000378:metabolism; D002645:Chickens / Q000378:metabolism*; D003051:Cochlea / Q000196:embryology / Q000378:metabolism*; D051345:Destrin; D006198:Hair Cells, Auditory / Q000378:metabolism; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D012016:Reference Values; D014018:Tissue Distribution
D051339:Actin Depolymerizing Factors; D000199:Actins; C495824:DSTN protein, human; D051345:Destrin; D008840:Microfilament Proteins; C118067:WDR1 protein, human