title: Balancing cell numbers during organogenesis: Six1a differentially affects neurons and sensory hair cells in the inner ear.
abstract: 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.
authors: Leslie and Susan Gonda Cell Biology and Genetics Division, House Research Institute, Los Angeles, CA 90057, USA. obricaud@hei.org
authors: Olivier
authors: O
authors: Bricaud
authors: Andres
authors: A
authors: Collazo
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D007758:Ear, Inner / Q000166:cytology / Q000196:embryology*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006198:Hair Cells, Auditory / Q000166:cytology* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C498351:Six1 protein, zebrafish; D014157:Transcription Factors; D029961:Zebrafish Proteins