Math1 regulates development of the sensory epithelium in the mammalian cochlea.
The transcription factor Math1 (encoded by the gene Atoh1, also called Math1) is required for the formation of mechanosensory hair cells in the inner ear; however, its specific molecular role is unknown. Here we show that absence of Math1 in mice results in a complete disruption of formation of the sensory epithelium of the cochlea, including the development of both hair cells and associated supporting cells. In addition, ectopic expression of Math1 in nonsensory regions of the cochlea is sufficient to induce the formation of sensory clusters that contain both hair cells and supporting cells. The formation of these clusters is dependent on inhibitory interactions mediated, most probably, through the Notch pathway, and on inductive interactions that recruit cells to develop as supporting cells through a pathway independent of Math1. These results show that Math1 functions in the developing cochlea to initiate both inductive and inhibitory signals that regulate the overall formation of the sensory epithelia.
Woods
Chad
C
Section on Developmental Neuroscience, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Porter Neuroscience Research Center, Building 35, Bethesda, Maryland 20892, USA.
Montcouquiol
Mireille
M
Kelley
Matthew W
MW
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D003051:Cochlea / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism*; D004848:Epithelium / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism*; D006198:Hair Cells, Auditory / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D014157:Transcription Factors / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D014157:Transcription Factors; C500943:Atoh1 protein, mouse