MOLECULAR STUDIES OF GROWTH FACTORS DURING DEVELOPMENT

Project Details

Description

Peptide growth factors such as nerve growth factor (NGF) and epidermal
growth factor (EGF) have well-defined effects on specific populations of
embryonic and adult cells. Despite extensive biochemical characterization
of these molecules and their effects on cells expressing NGF and EGF
receptors, essentially nothing is known about their physiological sites of
synthesis during development. In addition, although abnormal synthesis of
these factors has been implicated in the pathology of specific inherited
diseases such as neurofibromatosis, direct evidence has not yet appeared.
In this proposal, we outline our plans to use recently isolated recombinant
DNA probes to EGF and to the B-subunit of NGF to address these questions. 1. We will determine the levels of B-NGF and EGF mRNA in polyA-RNA extracts
of embryonic and adult tissues. We will use solid-phase DNA-RNA
hybridization techniques to quantitate the levels of growth factor mRNA
present in these extracts and compare the levels of these mRNA throughout
development. 2. We will concurrently locate specific cells types containing NGF and EGF
mRNA in embryonic and adult tissue sections using in situ hybridization.
We will focus on regions that have previously been suggested as putative
synthetic sites for these growth factors or that contain EGF and NFG mRNA
as determined by solid-phase DNA-RNA hybridization studies. 3. We will determine whether B-NGF mRNA and EGF mRNA are present in
neurofibromas and localize specific cells containing these growth factors
with in situ hybridization. We will quantitate the levels of growth factor
mRNA present in different neurofibroma types including stable and rapidly
growing neurofibromas, plexiform neurofibromas, and acoustic neuromas. Taken together, these studies will allow us to determine when NGF and EGF
gene expression normally occurs during embryogenesis and whether altered
growth factor mRNA levels are associated with specific neurofibromatoma
types.
StatusFinished
Effective start/end date4/1/8511/30/02

Funding

  • National Institutes of Health
  • National Institutes of Health: $266,947.00
  • National Institutes of Health: $243,913.00
  • National Institutes of Health: $312,195.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $247,431.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $288,792.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $150,556.00
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Neuroscience(all)

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