Project: Research project

Project Details


A major effort in contemporary biological research is to identify loci
that control developmental decisions. In addition, disturbance of the
normal differentiation process can contribute to tumorigenesis.
Determining the key regulatory mechanisms involved in generating and
maintaining the differentiated state is important for understanding both
normal development and disease. This is a proposal to investigate the control of cell type determination
in mammalian cells. By utilizing myoblast cell lines grown in vitro, and
a combined somatic cell and molecular genetic approach, the regulation of
the MyoD family of myogenic regulatory genes will be analyzed.
Intertypic hybrids will be assayed for activation and repression of
myogenesis. Genetic studies of this nature have been utilized to
identify positive and negative regulatory interactions in a number of
experimental systems. This project has four goals: 1) define the role of negative regulation of
MyoD in 10T1/2 X fibroblast hybrids, 2) determine whether additional
fibroblast chromosomes activate muscle, fat, or cartilage phenotypes in
1OT1/2 cells, 3) determine whether MyoD is repressed in cis or in trans
in 1OT1/2 cells, and 4) examine the genetic basis of extinction in 1OT1/2
X L6 myoblast hybrids. By identifying and ultimately isolating these
unique regulators, we can begin to define the genetic mechanisms involved
in the determination and differentiation of muscle cells. An
understanding of the regulatory circuits which control the myogenic
lineage will give important insights into the perturbations of gene
expression that result in abnormal muscle development and tumorigenesis.
Effective start/end date5/1/934/30/02


  • National Institutes of Health: $240,799.00
  • National Institutes of Health: $233,785.00


  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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