Disease relevance of ft

• Recessive lethal mutations of the lethal(2)giant discs (l(2)gd) and lethal(2)fat (l(2)ft) loci of Drosophila melanogaster cause imaginal disc hyperplasia during a prolonged larval stage [1].

High impact information on ft

• It has thus been suggested that Ft and Ds serve not as adhesion molecules, but as receptor and ligand in a poorly understood signaling pathway [2].
• In genetic tests, ft behaves as a suppressor of Wg signaling [3].
• The protocadherins Fat (Ft) and Dachsous (Ds) are required for several processes in the development of Drosophila, including controlling growth of imaginal discs, planar cell polarity (PCP) and the proximodistal patterning of appendages [2].
• We show that fj interacts genetically with ft and ds in planar polarity and proximodistal patterning [4].
• This Ft-Ds signaling model is based on mutant loss-of-function phenotypes, leaving open the question of whether Ds is instructive or permissive for PCP [5].

Biological context of ft

• Double mutant combinations with alleles of other genes, e.g. of the Epidermal growth factor receptor (DER) pathway, modify ft clonal phenotypes, indicating that adhesiveness is modulated by intercellular signalling [6].
• Mutant ft cells show, in addition, smaller cell sizes during proliferation and abnormal cuticular differentiation, which reflect cell membrane and cytoskeleton anomalies, which are not modulated by the DER pathway [6].
• It was recently suggested that a proximal to distal gradient of the protocadherin Dachsous (Ds) acts as a cue for planar cell polarity (PCP) in the Drosophila wing, orienting cell-cell interactions by inhibiting the activity of the protocadherin Fat (Ft) [5].
• We show that Ft and Ds mediate preferentially heterophilic cell adhesion in vitro, and that each stabilizes the other on the cell surface [5].
• Ft can regulate Hippo phosphorylation, a measure of its activation, in tissue culture [7].

Anatomical context of ft

• Gap junction distribution in the Drosophila wing disc mutants vg, l(2)gd, l(3)c43hs1, and l(2)gl4 [8].

Other interactions of ft

• We propose that Fj may act in the Golgi to regulate the activity of Ft and Ds [4].
• The comb gap (cg) mutation, which also interacts with ds, greatly enhances the tendency of imaginal discs from l(2)gd larvae to duplicate as they overgrow [1].

References