Contact Information:
Beth Israel Deaconess Medical Center
RW 663
330 Brookline Avenue
Boston, MA 02215
phone: 617-667-3894
fax: 617-667-2913
ssokol@caregroup.harvard.edu
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Research Summary
We would like to learn how developmental polarity is acquired and how cells differentiate and assemble into tissues in the vertebrate embryo, using the frog Xenopus laevis as an experimental system. Our primary interests are focused on Wnt proteins, extracellular signaling factors related to the Wnt1 proto-oncogene product. In addition to determining cell fate, Wnt proteins function to control cell and tissue polarity. Besides its role in a variety of developmental processes, proper Wnt signaling is required to regulate normal cell growth. Many components of the Wnt pathway are mutated in a number of breast and skin tumors, colon carcinomas and melanomas. Despite the importance of Wnts in embryogenesis and in cancer, Wnt signal transduction had not been completely defined. Our previous work demonstrated the structural and functional conservation of the Wnt pathway in vertebrates, and elucidated the essential role for the homeobox gene Siamois, a direct target of Wnt signaling, in Spemann organizer formation. One of the main concepts developed by our group and well accepted by workers in the field is the finding that early Wnt signaling cooperates with mesoderm inducing factors of the TGFbeta family to give rise to the Spemann organizer and to specify dorsal development in vertebrates. Our current studies are aimed at identification of new components of the Wnt signaling pathway and their roles in vertebrate axis specification and tissue patterning.
Another major area of our interests is neural induction and anteroposterior axis specification. Early events leading to neural tissue development are controlled by the Spemann organizer, however, molecular mechanisms operating during induction and anteroposterior patterning of the neural tissue remain to be elucidated. We wish to understand signaling processes leading to neural induction by studying early transcriptional responses to neural induction. At present, we have cloned the promoter of Zic3, one of the early response genes expressed in presumptive neuroectoderm, and identified a novel enhancer element that is responsible for its activity. Using transgenic Xenopus laevis carrying a Zic3 promoter-GFP reporter, we will study the signals controlling its expression in vivo. We plan to isolate transcription factors that bind and regulate the Zic3 promoter and identify embryonic signals responsible for regulation of this promoter. In addition to studying intracellular events leading to neural development, we investigate changes in cell shape and morphogenetic behavior that accompany neural induction during gastrulation. We hope to understand the sequence of events that underlie different organizer activities, including neural induction, anteroposterior axis specification and control of cell movements during gastrulation.
Selected Publications
Gloy, J., Hikasa, H., and Sokol S. Y. (2002). A novel protein, Frodo, interacts with Dishevelled to transduce Wnt signals. Nature Cell Biol. (in press).
Lisovsky, M., Itoh, K., and Sokol S. Y. (2002). Induction of apoptosis by Frizzled receptors Curr. Biol. 12, 53 - 58.
Sokol, S. Y. (2000). A role for Wnts in morphogenesis and tissue polarity. Nature Cell Biol., 2, E124-E126.
Itoh, K., and Sokol, S. Y. (1999). Axis determination by inhibition of Wnt signaling in Xenopus. Genes Dev. 13, 2328-2336.
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