Program of the 2001 International Worm Meeting - Sternberg Lab ...

3
further the biological relevance of the puncta
observed in anterior nuclei specifically.
4. Specification of Organ Identity by
the C. elegans FOXA homologue
PHA-4.
Jeb Gaudet, Michael Horner, Susan
E. Mango
Huntsman Cancer Institute, 2000 Circle of
Hope, University of Utah, Salt Lake City, UT,
84112
During development, cells acquire distinct cell
fates in response to a host of regulators, many of
which encode transcription factors. A
longstanding issue has been the nature of the
target genes controlled by these transcriptional
regulators: do they activate a few genes at the
top of a hierarchy, or control many genes that
function at multiple stages throughout
development? This question has been difficult to
resolve because few direct targets have been
identified.
To address how transcription factors influence
cell fate decisions, we are studying the role of
the fork head box protein PHA-4 during
pharynx development. In embryos that lack
pha-4 activity, cells that would normally
become part of the pharynx develop as ectoderm
instead. Conversely, ectopic expression of pha-4
produces excess pharyngeal cells at the expense
of other cell types. Because pha-4 normally
functions in pharyngeal cells irrespective of the
cells’ lineage or cell type, we propose that pha-4
endows cells with pharyngeal organ identity.
We have used a microarray chip approach to
identify genes selectively expressed in the
pharynx and have analyzed those genes to
determine which are direct PHA-4 targets. We
took advantage of maternal effect mutants that
produce embryos with excess (par-1) or no
(skn-1) pharyngeal cells to identify candidate
pharyngeal genes. Included among our positive
clones were most (>70%) genes known to be
expressed in the pharynx, indicating that our
approach worked well.
Three lines of evidence suggest that PHA-4
directly activates most or all
pharyngeally-expressed genes. First, we
examined the pharynx-specific expression of a
random set of microarray positives and found
that the expression of each depended on one or
more predicted PHA-4 binding sites. Second,
4