Xing Dai
Ph.D., University of Chicago, Chicago, Illinois, 1995
Department of Biological Chemistry
University of California, Irvine
Irvine, CA 92697
(949) 824-3101, 7409
xdai@uci.edu
UCI Faculty Profile: Xing Dai
Research Interests:
Transcriptional control of epithelial differentiation in mice, stem cells, movo genes, Wnt-beta-catenin-LEF/TCF signaling
The development, maintenance, and regeneration of complex mammalian tissues involve multi-tiered control mechanisms including those regulating commitment to different cell lineages and cellular differentiation along a particular lineage. Self-renewing tissues such as skin and testis provide excellent model systems to study the genetic pathways underlying such control mechanisms, as they contain stem cells that persist throughout the life span of an animal and possess long-term proliferation and differentiation potential. Upon receiving certain developmental and/or environmental cues, stem cells in these tissues commit to differentiation, undergo transient amplification, and subsequently cease proliferation to enter the program of terminal differentiation to produce highly specialized cells with essential biological functions. In my laboratory, we focus on the role of ovo family of genes, which encode zinc finger transcription factors and include members that have been placed downstream of the Wnt-beta-catenin-LEF/TCF and TGFbeta/BMP signaling pathways, in epithelial proliferation and differentiation. The long-term goals of my research program are to identify key upstream and downstream players in the movo (mouse ovo) -regulatory pathway, to characterize the functions of these players, and to elucidate their biochemical and genetic relationships with movo. To achieve these goals, we use a combinatory approach involving genetics, developmental biology, biochemistry, molecular biology, and cell biology. We have ongoing projects in the following areas:
1. Characterizing the cellular and molecular mechanisms of movo function in development and differentiation.
We have shown that movo1 is required for the development and differentiation of multiple tissues including skin, testis, kidney, and the urogenital tract. Our recent gene targeting studies have uncovered a role for movo2 in early embryonic development, particularly in the neuroepithelium. Using histological, cell biological, as well as gene expression analyses, we have shown that movo1 plays a role in growth suppression. Current studies focus on identifying downstream targets of movo1 and examining whether a growth inhibitory function is common to all movo genes including movo2. We do so using an array of techniques including in vitro protein-DNA interaction assays, cell culture reporter assays, primary cell cultures, and chromatin immunoprecipitation (CHIP) assays. Furthermore, we employ genetic approaches, such as creating and analyzing movo1/movo2 double mutant mice, to address any possible functional compensation/redundancy between these genes.
2. Characterizing the role of mpygo2, a newly identified core component of the Wnt-beta-catenin-LEF/TCF signaling pathway, in epithelial development and differentiation. The canonical Wnt signaling regulates ovo genes in flies and mice and has been shown to play important roles in epithelial stem cell maintenance, proliferation, differentiation, and tumorigenesis. We have cloned and characterized mpygo2, one of two pygo genes in mice that shows a broad expression spectrum consistent with the wide-spread involvement of Wnt signaling in development. Current studies focus on using genetically altered mutant mice to understand the role of mpygo2 in Wnt signaling and in normal and malignant epithelial development. We also collaborate with the Waterman lab on campus to study the role of mpygo2 in the beta-catenin-LEF/TCF transcriptional complex.
Selected Publications:
Glucksmann-Kuis, M. A., Dai, X., Markiewicz, P., and Rothman-Denes, L. B. (1996). "E. coli SSB activation of N4 virion RNA polymerase: specific activation of an essential DNA hairpin required for promoter recognition". Cell 84, 147-154.
Dai, X., Greizerstein, M., Nadas-Chinni, K., and Rothman-Denes, L. B. (1997). "Supercoil-induced extrusion of a regulatory DNA hairpin". Proc. Natl. Acad. Sci. USA 94, 2174-2179.
Dai, X. and Rothman-Denes, L. B. (1998). "Sequence and DNA strucutral determinants of N4 virion RNA polymerase-promoter recognition".
Genes & Development 12, 2782-2790.
Dai, X., Schonbaum, C., Degenstein, L., Bai, W., Mahowald, A., Fuchs, E. (1998). "The ovo gene required for cutcle formation and oogenesis in flies is involved in hair formation and spermatogenesis in mice". Genes & Development 12, 3452-3463.
Li, B., Mackay, D. R., Dai, Q., Li, T. W. H., Nair, M., Fallahi, M., Schonbaum, C., Fantes, J., Mahowald, A., Waterman, M. L., Fuchs, E., and Dai, X.(2002). The LEF1/b-catenin complex activates movo1, a mouse homolog of Drosophila ovo gene required for epidermal appendage differentiation. Proc. Natl. Acad. Sci. USA 99, 6064-6069.
Kaufman, C. K., Zhou, P., Pasolli, H. A., Rendl, M., Bolotin, D., Lim, K. C., Dai, X., Alegre, M. L., and Fuchs, E. (2003). GATA-3: an unexpected regulator of cell lineage determination in skin. Genes & Development 17, 2108-2122.
Li B, Nair M, Mackay DR, Bilanchone V, Hu M, Fallahi M, Song H, Dai Q, Cohen PE, Dai X. (2005). Ovol1 regulates meiotic pachytene progression during spermatogenesis by repressing Id2 expression. Development 132:1463-73.
Mackay, D. R., Hu, M., Li, B., Rh¨¦aume, C., and Dai, X. (2006). The mouse Ovol2 gene is required for cranial neural tube development. Developmental Biology 291(1):38-52.
Nair, M., Teng, A., Bilanchone, V., Agrawal, A., Li, B. and Dai, X. Ovol1 controls the growth arrest of embryonic epidermal progenitor cells and represses c-Myc transcription. JCB 173, 253-264.
