Inhibitors of differentiation and DNA binding (Ids) regulate Math1 and hair cell formation during the development of the organ of Corti.
The basic helix-loop-helix (bHLH) transcription factor Math1 (also called Atoh1) is both necessary and sufficient for hair cell development in the mammalian cochlea (Bermingham et al., 1999; Zheng and Gao, 2000). Previous studies have demonstrated that a dynamic pattern of Math1 expression plays a key role in regulating the number and position of mechanosensory hair cells. However, the factors that regulate the temporal and spatial expression of Math1 within the cochlea are unknown. The bHLH-related inhibitors of differentiation and DNA binding (Id) proteins are known to negatively regulate many bHLH transcription factors, including Math1, in a number of different systems. Therefore, Id proteins are good candidates for regulating Math1 in the cochlea. Results from PCR and in situ hybridization indicate that Id1, Id2, and Id3 are expressed within the cochlear duct in a pattern that is consistent with a role in regulation of hair cell development. In particular, expression of Ids and Math1 overlapped in cochlear progenitor cells before cellular differentiation, but a specific downregulation of Id expression was observed in individual cells that differentiated as hair cells. In addition, progenitor cells in which the expression of Ids was maintained during the time period for hair cell differentiation were inhibited from developing as hair cells. These results indicate a key role for Ids in the regulation of expression of Math1 and hair cell differentiation in the developing cochlea.
Jones
Jennifer M
JM
Section on Developmental Neuroscience, Porter Neuroscience Center, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
Montcouquiol
Mireille
M
Dabdoub
Alain
A
Woods
Chad
C
Kelley
Matthew W
MW
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation; D018076:DNA, Complementary / Q000235:genetics; D018274:Electroporation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006198:Hair Cells, Auditory / Q000166:cytology* / Q000378:metabolism; D051798:Inhibitor of Differentiation Protein 1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051797:Inhibitor of Differentiation Protein 2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051796:Inhibitor of Differentiation Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009924:Organ Culture Techniques; D009925:Organ of Corti / Q000166:cytology / Q000196:embryology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D018076:DNA, Complementary; D051798:Inhibitor of Differentiation Protein 1; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; C500943:Atoh1 protein, mouse; C497455:Idb1 protein, mouse; C497452:Idb2 protein, mouse; C067679:Idb3 protein, mouse