Ming-Jer Tsai, Ph.D.
Molecular & Cellular Biology
Nuclear orphan receptor COUP-TFII and organogenesis
Ming-Jer Tsai, Ph.D. and Sophia Y. Tsai, Ph.D., both received the award for their research in dissecting the in vivo function of nuclear orphan receptors, COUP-TFI and COUP-TFII. COUP-TFs have been shown to play important roles in development. COUP-TFI null mice exhibit defects in axon guidance, in cortical layer formation, in brain regionalization, and axon myelination. These results indicate that COUP-TFI is critical for the function of the central and peripheral nervous system. COUP-TFII null mice display defects in angiogenesis and heart development and die before E 10.0. Tissue specific knock out of COUP-TFII in the stomach shows posterior transformation and aberrant muscle differentiation. Both phenotypes implicate COUP-TFII as a mediator of the hedgehog signaling pathway. In addition, haploid insufficiency is shown in COUP-TFII heterozygous mutants. The expression patterns and the phenotypes exhibited by the COUP-TFII mutants suggest that COUP-TFII is essential for organogenesis in tissues requiring mesenchymal-epithelial interactions. Taken together, the above findings indicate that COUP-TFI and COUP-TFII serve vital functions during development and raise the possibility of future ligand based therapy for disease treatment.
Dr. Tsai and Tsai’s research was based on the following publications:
Pereira FA, Qiu Y, Zhou G, Tsai MJ, Tsai SY. The orphan nuclear receptor COUP-TFII is required for angiogenesis and heart development. Genes Dev. 1999 Apr 15;13(8):1037-49.
Zhou C, Qiu Y, Pereira FA, Crair MC, Tsai SY, Tsai MJ. The nuclear orphan receptor COUP-TFI is required for differentiation of subplate neurons and guidance of thalamocortical axons. Neuron. 1999 Dec;24(4):847-59.
Huang HP, Liu M, El-Hodiri HM, Chu K, Jamrich M, Tsai MJ. Regulation of the pancreatic islet-specific gene BETA2 (neuroD) by neurogenin 3. Mol Cell Biol. 2000 May;20(9):3292-307.
Zhou C, Tsai SY, Tsai MJ. COUP-TFI: an intrinsic factor for early regionalization of the neocortex.Genes Dev. 2001 Aug 15;15(16):2054-9.