Research Officer The University of Hong Kong Hong Kong, China
Abstract: Cell fate determination is orchestrated by precise key regulators expression. Sox2, one of the stemness factors, is both necessary and sufficient to drive prosensory fate during inner ear development. Through the study of the genomes of two Sox2 hypomorphic mutants, Sox2Ysb and Sox2Lcc, novel early acting otic regulatory elements were identified in the disrupted region downstream of Sox2 in these mutants. The data indicate the dynamic otic expression of Sox2 is controlled by multiple temporal- and spatial- specific enhancers. We have demonstrated the dosage-dependent requirement of Sox2 on otic prosensory lineage decision. Reduced SOX2 level does not only change prosensory cell fate to a nonsensory ES/ED progenitor-like cell fate, as evidenced by the molecular signatures of the mutant cells starting from early OV stage, but also promotes apoptosis in mutant cells at later stage. Additionally, we showed BMP/TGFbeta signalling is required for both activating and restricting Sox2 expression during early and late otic development, respectively. The results are consistent with a temporal-specific role of Sox2 expression, under many delicate layers of both cis and trans regulations.
Funding Source: Health and Medical Research Fund #05163176, Research Grants Council and University Grants Council of Hong Kong (HKU7385/02M; AoE/M-04/04), National Institute of Health USA (RO1 DC 005590) and the Medical Research Council.
