The Specificity protein (Sp) transcription factor family includes many proteins that play critical roles in normal development and disease progression in vertebrates. For example, Sp protein overexpression is a negative prognostic factor for the survival of patients diagnosed with various types of cancer. The Sp transcription factors are characterized by the presence of three highly conserved C-terminal C2H2 zinc finger domains that form the DNA binding domain, and are known to bind to GC rich elements in the DNA. This study reports the functional characterization of the C.elegans Sp gene,
sptf-3, and elucidates its potential role in modulating Wnt regulated processes. We isolated
sptf-3(
gu85) in a genetic screen performed to identify partners that function with EGL-38, a Pax factor, in regulating the expression of a target gene
lin-48. SNP mapping placed the
sptf-3(
gu85) mutation on LGI and sequencing of the genomic DNA revealed that it is a mutant allele of the Sp gene Y40B1A.4. We find that
gu85 is a missense mutation that affects the DNA binding domain and abolishes the DNA binding ability of the protein. In addition,
sptf-3(
gu85) mutant animals show a wide range of developmental defects that are similar to these seen in Wnt pathway mutants. Specifically, mutant hermaphrodites exhibit the Biv phenotype similar to
lin-17(frizzled) and
lin-18(RTK) mutants. We have used vulval cell markers that suggest that the Biv phenotype results from reversal of the P7.p cell lineage characteristic of the Wnt pathway mutants. In addition,
sptf-3(
gu85) mutant animals exhibit P12 to P11 cell fate transformations, also characteristic of
lin-17 mutants. This data is supported by evidence that the Sp transcription factors are involved in regulating Wnt pathway function in both invertebrates and vertebrates. We are currently working on dissecting the mechanism of action of the
sptf-3 gene in the development of several organs that are responsive to the Wnt pathway and are attempting to determine how this gene functions with the Wnt pathway to influence development.