atp2b1a regulates Ca2+ export during differentiation and regeneration of mechanosensory hair cells in zebrafish

The molecular mechanisms of development of mechanosensory hair cells have been tackled successfully due to in vivo studies in the zebrafish lateral line. The enhancer trap (ET) transgenic line, SqET4 was instrumental in these studies even despite a lack of a link of its GFP expression pattern to a particular gene(s). We mapped the Tol2 transposon insertion of the SqET4 transgenics onto Chr. 4 next to a gene encoding Atp2b1a (Pmca1) - one of the four PMCAs acting to export Ca2+ from a cell. atp2b1a expression recapitulates that of GFP during the development of mechanoreceptors of the inner ear and lateral line. atp2b1a expression correlates with the regeneration of these cells. Thus, SqET4 represents the Tg:atp2b1a-GFP line, which links Ca2+ metabolism and the differentiation of mechanoreceptors. The morpholino-mediated knockdown of atp2b1a blocks Ca2+ export and affects the division of hair cell progenitors, resulting in their accumulation. Under the control of a master gene of hair cells, Atoh1a, Atp2b1a functions during progenitor cell proliferation and hair cell differentiation. Given the similarity between the phenotypes of atp2b1a morphants and embryos treated with the pan-PMCA inhibitor 5(6)-carboxyeosin, Atp2b1a emerges as member of the Atp2b family responsible for Ca2+ export during the development of hair cells.