The specification of cell-fate by the integration of multiple signaling pathways is an emerging paradigm in developmental gene regulation. At least two cases of signal integration are necessary in C. elegans for correct cell fate specification. In the hermaphrodite vulva, integration EGF and Wnt pathway signals are required for specification of the vulval precursor cells. In the P12 neuroectoblast cell in the tail, integration of EGF and Wnt pathway signals are again required to effect P12 fate. In both these cases, integration of the two pathways results in the activation of a hox gene, lin-39 in the vulva and egl-5 in P12. The goal of this proposal is to define and compare the modes of signal integration in these two cases that lead to hox gene activation.
I aim to achieve these goals by isolating upstream factors required for correct lin-39 and egl-5 expression and by defining cis-acting elements in lin-39 and egl-5 required for their endogenous expression pattern. The important role the highly conserved EGF/RAS/RAF and Wnt pathways play in animal cell proliferation and differentiation necessitates their understanding. It has been found that up to ninety percent of certain types of carcinomas have mutated RAS genes, thus it is essential we understand how these pathways work in concert in normal differentiation in order that we can understand the oncogenic consequences due to alterations in these pathways.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM020455-03
Application #
6518849
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Tompkins, Laurie
Project Start
2000-07-01
Project End
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
3
Fiscal Year
2002
Total Cost
$44,212
Indirect Cost
Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
078731668
City
Pasadena
State
CA
Country
United States
Zip Code
91125