We study the signaling and transcriptional regulatory networks that
underlie the development of the heart and body wall muscles of the
Drosophila embryo. Mesodermal progenitor cells are determined by the
combined inputs of multiple intercellular signals, including those
initiated by Wnt and BMP family members, as well as those mediated by
the receptor tyrosine kinase (RTK)/Ras and Notch (N) pathways. The
specification of some progenitors depends on all of these signals,
raising two important questions: (1) how are the various inputs
integrated to generate a unique response, and (2) do the signals act
separately or does cross-talk occur among them? We have found that
Wnt, BMP and Ras activities converge at the transcriptional level.
Furthermore, these generic signals yield mesoderm-specific outputs by
functioning together with tissue-restricted transcription factors to
regulate the expression of at least one muscle and cardiac progenitor
identity gene. In addition, the activities of the Ras and N pathways
are dynamically modulated by reciprocal cross-talk and feedback
mechanisms. Our characterization of one signal-responsive, mesoderm-
specific transcriptional enhancer has enabled us to develop a global
computational approach for the identification of structurally and
functionally related cis-regulatory modules. Work is in progress to
use expression profiling data and comparative genomics to refine this
in silico approach in order to expand our understanding of the
genetic regulatory codes that orchestrate embryonic development. We
are also combining classical genetics with DNA microarray analysis of
genome-wide expression patterns to characterize the transcriptional
responses to various combinations of intercellular signals. This work
benefits from our ability to focus on particular subsets of
mesodermal cells isolated by flow cytometry after targeted expression
of fluorescent protein markers.
