Our laboratory is concerned with the molecular and cellular events involved in cell specification in the early vertebrate embryo; a process by which multi-potent precursor cells become progressively restricted in developmental potential and eventually become committed to a single developmental lineage or cell type. Cells destined to enter the myogenic lineage progress through a series of cellular and molecular trans-formations leading ultimately to the formation of mature myocytes with highly ordered, contractile cytoplasm. Skeletal muscle in the vertebrate body arises exclusively from the somites, transient epithelial structures that are responsible for many aspects of vertebrate body development including segmentation. Using somite transplantation, dye-injection and molecular experiments we are analyzing the cellular and molecular changes involved in the determination and differentiation of skeletal muscle precursor cells as they emerge from the developing somite in vivo.
Presumptive myocardial cells, which arise from non-somitic regions of the early embryo, undergo a series of molecular and cellular transformations during their specification that is entirely different from that described above for skeletal muscle prescursor cells. We have characterized a new transcription factor family, TEF-1 whose members are required for the transcription of the majority of known cardiac-specific genes. Our current efforts are directed toward understanding how different TEF-1 factors act on transcription by binding to specific DNA sites in combination with polyADP-ribose polymerase (PARP) to repress and activate genes in a cell-selective manner.
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Selected Publications
Caplan, A.I. and C.P. Ordahl. (1978) Irreversible gene repression model for control of development. Science. 201(4351): 120-30.
Ordahl, C.P., E. Berdougo, S.J. Venters, and W.F. Denetclaw, Jr. (2001) The dermomyotome dorsomedial lip drives growth and morphogenesis of both the primary myotome and dermomyotome epithelium. Development. 128(10): 1731-44.
Huang, K., W.E. Tidyman, K.U. Le, E. Kirsten, E. Kun, and C.P. Ordahl. (2004) Analysis of nucleotide sequence-dependent DNA binding of poly(ADP-ribose) polymerase in a purified system. Biochemistry. 43 (1): 217-23.
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