Balancing cell numbers during organogenesis: Six1a differentially affects neurons and sensory hair cells in the inner ear

While genes involved in the differentiation of the mechanosensory hair cells and the neurons innervating them have been identified, genes involved in balancing their relative numbers remain unknown. Six1a plays a dual role by promoting hair cell fate while inhibiting neuronal fate in these two lineages. Genes homologous to six1a act as either transcriptional activators or repressors, depending on the partners with which they interact. By assaying the in vivo and in vitro effects of mutations in presumptive protein-protein interacting and DNA-binding domains of Six1a, we show that, in the developing zebrafish inner ear, Six1a promotes hair cell fate by acting as a transcriptional activator and inhibits neuronal fate by acting as a transcriptional repressor. We also identify several potential partners for Six1a that differ between these two lineages. The dual role of Six1a in the developing otocyst provides a mechanism for balancing the relative number of hair cells and neurons during organogenesis of the inner ear. [Display omitted] ► Six1a function balances the number of hair cells and neurons in the inner ear. ► Six1a acts as a transcriptional repressor in the neuronal lineage. ► Six1a acts as a transcriptional activator in the sensory hair cell lineage. ► Six1a function in the neuronal lineage likely involves chromatin remodeling.