The Journal of Neuroscience, January 11, 2006, ():
Inhibitors of Differentiation and DNA Binding (Ids) Regulate Math1 and Hair Cell Formation during the Development of the Organ of Corti
J. Neurosci. Jones et al.
26: 550
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Supplemental Figure 1. Dynamic interactions between Math1 and Ids regulate determination of progenitor cell fate in the developing cochlea. A. Prior to determination of cell fate, progenitor cells within the prosensory domain express both Math1 (blue) and Ids (orange). The presence of Ids in progenitor cells prevents Math1 from activating its own expression to a sufficient level to induce commitment to the hair cell fate. As development continues, a subset of progenitors down-regulate Id expression, leading to an increase in Math1 expression (blue cell with orange dots) and commitment to the hair cell fate. Finally, as individual cells continue to develop as hair cells, they begin to express two Notch ligands, Jag2 and Dll1 (red lines). Expression of Jag2/Dll1 leads to activation of Notch (green lines) in neighboring cells and to the downstream target genes HES1 and HES5 (green dots). The combined expression of Ids (orange) and HES1/HES5 leads to a complete down-regulation of Math1 in these cells. Subsequently inductive signals generated by developing hair cells recruit these cells to develop as supporting cells. B. At the molecular level, in progenitor cells Math1 and Ids compete for form heterdimers with E47. Math1/E47 heterodimers, when available, will bind to the E Box in the Math1 promoter region, leading to increased expression of Math1. In cells that will develop as hair cells, there is a decrease in expression of Ids. As a result, the ratio of Math1/E47 heterodimers increases, leading to increased activation of the Math1 E Box promoter and Math1 expression. In contrast, in cells located adjacent to hair cells, Id expression persists. Following activation Notch signaling, there is an increase in HES expression. The combination of Id/E47 and HES/E47 heterodimers, leads to a decrease in the number of Math1/E47 heterdimers and ultimately to a complete down-regulation of Math1 promoter activity. These cells will develop as supporting cells.
