Dynamic gene expression by putative hair-cell progenitors

Hearing loss is most commonly caused by the destruction of mechanosensory hair cells in the cochlea. This condition is usually permanent: despite the presence of putative hair-cell progenitors in the ear, hair cells are not naturally replenished in adult mammals. Unlike those of the mammalian ear, the progenitor cells of non-mammalian vertebrates can regenerate hair cells throughout life. The basis of this difference may lie in molecular dissimilarities that affect how progenitors respond to hair-cell death. To approach this issue we analyzed gene expression in hair-cell progenitors of the lateral-line system. We developed a transgenic line of zebrafish that expresses a red-fluorescent protein in the presumptive hair-cell progenitors known as mantle cells. Fluorescence-activated cell sorting from the skins of transgenic larvae, followed by microarray-based expression analysis, revealed a constellation of transcripts that are specifically enriched in these cells. Gene-expression analysis after hair-cell ablation uncovered a cohort of genes that are differentially regulated early in regeneration, suggesting possible roles in the response of progenitors to hair-cell death. These results provide a resource for studying hair-cell regeneration and the biology of sensory progenitor cells.

A schematic diagram (left) shows hair cells, surrounded by supporting cells, at the center of a neuromast. The putative precursors for hair-cell replenishment are mantle cells at the organ's perimeter. Fluorescence microscopy (right) reveals the selective labeling of hair cells with membrane-tethered green-fluorescent protein (GFP) and of mantle cells with mCherry.