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Natural and small molecule regulators of cardiogenesis
Author(s) -
Mercola Mark
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.523.4
Subject(s) - wnt signaling pathway , microbiology and biotechnology , biology , context (archaeology) , morphogenesis , transcription factor , notch signaling pathway , cellular differentiation , regeneration (biology) , cell signaling , signal transduction , computational biology , biochemistry , gene , paleontology
I will present our recent advances in understanding mediators of the Dkk1, Nodal and Notch pathways that control differentiation and cell cycle of cardiomyocytes as well as our high throughput screening approaches to identify small molecules that control cardiomyocyte differentiation and physiology. New structure/function studies of the Dkk family of secreted proteins will be presented demonstrating a novel signal that stimulates heart induction and tissue morphogenesis. Dkk proteins have been known solely as antagonists of Wnt activity because of their ability to disrupt the Wnt signaling complex; however, this new activity is independent of Wnt signaling. Second, it is possible to stimulate cell cycle entry of committed precursors through the actions of the Notch pathway, which functions in this context by both an RBP/CSL‐dependent transcriptional action and also by a novel activity that is indpendent of downstream transcription. Third, our high content screening (HCS) approach for stem cell differentiation has yielded several classes of novel synthetic compounds that promote early steps of ESC cardiogenesis will be presented. HCS strategies and phenotypic screening constitute a feasible chemical biological approach for the identification of cellular targets for discovery of drugs to enhance cardiomyocyte regeneration.