• Runyan, Raymond B (PI)

Project: Research project

Grant Details


The valves and septa of the adult heart are formed in large part from
embryonic "cushion tissue". A majority of congenital heart defects appear
to arise from the defective development of cushion tissue. The earliest
cellular events of cushion tissue formation are an
epithelial-to-mesenchymal cell transformation and the subsequent migration
of the mesenchyme into cell-free extracellular matrix. Both of these
processes require the recognition of specific extracellular matrix (ECM)
molecules in order to proceed. A novel enzymatic mechanism of ECM recognition has recently been
demonstrated. Cell surface galactosyltransferase (GalTase) was shown to
function as a receptor during migration of another teratologically
sensitive cell population, the nerual crest. Evidence is shown that the
same enzyme is present during cushion tissue formation and that
morphogenetic mouse mutants which display elevated levels of this enzyme
have concomitant defects in cushion tissue development. This proposal
examines the role of GalTase during the earliest cellular events of cushion
tissue formation. Further experiments are proposed to evaluate the
relationship of this particular receptor mechanism to others which may be
present. To accomplish these studies, a variety of independent probes will be
employed which are specific for this enzyme. Experiments will define the
distribution and occurrence of the enzyme during cushion tissue formation.
Specific cellular events will be isolated in culture and examined as the
enzyme is perturbed by modification, competition, and catalysis. The
substrate(s) recognized by this cell surface receptor will be identified by
radioactive labeling. One other glycosyltransferase has been identified in
the heart and will also be examined. Finally, chemical cross-linking of
cushion tissue cells and cardiac TCM will be performed to examine the
variety of cell:matrix interactions which may be occurring. These studies
will define a specific molecular mechanism and will aid in our
understanding of congenital malformations.
Effective start/end date9/30/861/31/95


  • National Institutes of Health: $60,541.00


  • Medicine(all)


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