The Hedgehog (Hh) and Wingless (Wg) signaling pathways play important roles in animal development. The activities of the two pathways depend on each other during Drosophila embryogenesis. In the embryonic segment, Wg is required in anterior cells to sustain Hh secretion in adjacent posterior cells. Hh input in turn is necessary for anterior cells to maintain wg expression. The Hh and Wg pathways are mediated by the transcription factors Cubitus interruptus (Ci) and Pangolin/TCF (Pan), respectively. Coincidentally, pan and ci are adjacent genes on the fourth chromosome in a head-to-head orientation. Our genetic and in situ hybridization data indicate that ci(D) is a mutation affecting both ci and pan. Molecular analysis revealed that the ci(D) allele is caused by an inversion event that swapped the promoter regions and the first exons of the two genes. The ci gene in ci(D) is controlled by the ubiquitous pan promoter and encodes a hybrid Ci protein that carries the N-terminal region of Pan. This domain has previously been shown to bind to the β-catenin homolog Armadillo (Arm), raising the possibility that Wg input, in addition to Hh input, modulates the activity of the hybrid Ci(D) protein. Indeed, we found that Wg signaling induces the expression of the Hh target gene patched (ptc) in ci(D) animals. We provide evidence that this effect depends on the ability of the Ci(D) protein to bind Arm. Genetic and molecular data indicate that wild-type Pan and Ci(D) compete for binding to Arm, leading to a compromised transduction of the Wg signal in heterozygous ci(D)/+ animals and to a dramatic enhancement of the gain-of- function activity of Ci(D) in homozygous mutants. Thus, the Hh and the Wg pathways are affected by the ci(D) mutation, and the Ci(D) fusion protein integrates the activities of both.
Schweizer, L., & Basler, K. (1998). Drosophila ci(D) encodes a hybrid Pangolin/cubitus interruptus protein that diverts the wingless into the Hedgehog signaling pathway. Mechanisms of Development, 78(1–2), 141–151. https://doi.org/10.1016/S0925-4773(98)00163-4