Sergei Sokol

..We discuss the relevance of these findings to existing models of Wnt signal transduction to the nucleus...

..This review focuses on recent progress in the understanding of context-dependent post-translational regulation of TCF function by Wnt signaling...

..Although the results of recent studies of the Wnt/β-catenin pathway in ES cells appear to be surprising and controversial, they converge on the same conserved mechanism that leads to the inactivation of TCF3-mediated repression...

..Themes that dominated the meeting included the need for precise control over each step of the signal transduction mechanism and developing therapeutics for diseases caused by altered Wnt-signaling...

..We conclude that PAR-1BY is required in the PCP branch and mediates Dsh membrane localization while PAR-1A and PAR-1BX are essential for canonical signaling to beta-catenin, possibly via targets other than Dishevelled...

..These findings suggest a molecular basis for the regulation of cell polarity by Frizzled and Dishevelled...

..These findings suggest that Stbm/Vangl2 functions to maintain cortical progenitors and regulates mitotic spindle orientation during asymmetric divisions in the vertebrate brain...

..These observations suggest a conserved mechanism for neuronal fate determination that might operate during asymmetric divisions of polarized neural progenitor cells...

..These results suggest a molecular link between Wnt5a and Lgl that is essential for apical constriction during vertebrate gastrulation...

..Furthermore, many Axin(DeltaC6/DeltaC6) embryos that were heterozygous for a beta-catenin null mutation survived to term, demonstrating that early lethality was due to failure to negatively regulate beta-catenin...

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..Highly conserved dynamic expression patterns of Frodo homologues indicate a similar function for these proteins in different vertebrates...

..abstract_text> ..

..Thus, studying the mechanisms of Wnt signal transduction, we hope to get insight into basic questions of axis specification and into molecular mechanisms of cancer. ..

..Since the Wnt pathways are inappropriately regulated in many cancers, the outcome of proposed experiments should provide insight into the key mechanisms of cell regulation as well as molecular origins of human cancer. ..

..The knowledge of the molecular pathways that involve MAK should allow the design of small molecules, which can modulate its enzymatic activity, and may lead to the development of new anti-cancer therapies. ..

..As the same signaling mechanisms operate multiple times during early embryonic development in all vertebrate embryos, the regulation of these processes should prove useful in the prevention and correction of human birth defects. ..

..Since the Wnt pathways are inappropriately regulated in many cancers, the outcome of proposed experiments should provide insight into the key mechanisms of cell regulation as well as molecular origins of human cancer. ..

..The knowledge of the molecular pathways that involve MAK should allow the design of small molecules, which can modulate its enzymatic activity, and may lead to the development of new anti-cancer therapies. ..

..Since Wnt pathways are activated in many human cancers, including colon carcinomas, melanomas and skin tumors, the proposed experiments are directly relevant to human disease. ..

..A role of pre-existing polarity within ectoderm in anteroposterior neural patterning will be also evaluated. These experiments will shed more light on our knowledge of anteroposterior patterning of the vertebrate central nervous system. ..

..Proposed studies will identify the components involved in this novel pathway and should decipher new ways of controlling cell number in development and in disease. ..