gammy legs, a PHD-containing protein, is required for Wingless signaling. D.S Parker , B.D Looyenga , J. Jemileh , K.M Cadigan. MCDB, University of Michigan, Ann Arbor, MI.

   We have identified a new component of Wingless (Wg, Wnt in vertebrates) signaling we call gammy legs (gam) in a misexpression screen for genes that antagonize a wg induced small eye phenotype. gam overexpression also gives phenotypes consistent with a block in Wg signaling in several additional tissues. We have created loss of function alleles that suggest gam is a core player in the Wg pathway. gam germ line clones have embryonic phenotypes very similar to that of wg null mutants. The same is true in somatic tissues; in wing, leg, eye and antennal imaginal discs reduction or removal of gam gives phenotypes consistent with a complete loss of Wg signaling. gam does not appear to be a direct target of Wg signaling as it is expressed at low levels ubiquitously and not in a wg dependent manner.
   Loss of function epistasis experiments indicate that gam is downstream of dAxin and is not required for Armadillo (Arm) nuclear import. Overexpression epistasis places gam downstream of a stabilized form of Arm. Consistent with this data, a transfected GFP Gam fusion resides in the nucleus of S2 cells. The Gam ORF contains two recognized motifs; an NLS and a PHD domain. The function of PHD domains is not yet understood but they are often found in transcription factors and chromatin remodeling proteins. Taken together these data hint that gam may play a role in transcriptional regulation of Wg target genes.
   We have also cloned two vertebrate gam homologues. When overexpressed in mammalian cell culture they antagonize expression of a Wnt dependent reporter gene indicating gam is functionally conserved in vertebrates. We conclude that gam is a conserved nuclear factor required for Wg/Wnt signal transduction. Our next aim is to identify interacting partners of Gam to begin to understand how gam may function at the molecular level.