Stem and progenitor cell proliferation are independently regulated by cell type-specific genes.

Regeneration and homeostatic turnover of solid tissues depend on the proliferation of symmetrically dividing adult stem cells, which either remain stem cells or differentiate based on their niche position. Here we demonstrate that in zebrafish lateral line sensory organs, stem and progenitor cell proliferation are independently regulated by two genes. Loss of impairs stem cell proliferation during development, while loss of disrupts hair cell progenitor proliferation but allows normal differentiation. Notably, can functionally replace , indicating that the respective effects of these Cyclins on proliferation are due to cell type-specific expression. However, even though hair cell progenitors differentiate normally in mutants, they are mispolarized due to and Emx2 downregulation. Thus, regulated proliferation ensures that equal numbers of hair cells are polarized in opposite directions. Our study reveals cell type-specific roles for genes in regulating the different populations of symmetrically dividing cells governing organ development and regeneration, with implications for regenerative medicine and disease.