Kakapo, a novel cytoskeletal-associated protein is essential for the restricted localization of the neuregulin-like factor, vein, at the muscle-tendon junction site

In the Drosophila embryo, the correct association of muscles with their spe cific tendon cells is achieved through reciprocal interactions between thes e two distinct cell types. Tendon cell differentiation is initiated by acti vation of the EGF-receptor signaling pathway within these cells by Vein, a neuregulin-like factor secreted by the approaching myotube. Here, we descri be the cloning and the molecular and genetic analyses of kakapo, a Drosophi la gene, expressed in the tendons, that is essential for muscle-dependent t endon cell differentiation. Kakapo is a large intracellular protein and con tains structural domains also found in cytoskeletal-related vertebrate prot eins (including plakin, dystrophin, and Gas2 family members). kakapo mutant embryos exhibit abnormal muscle-dependent tendon cell differentiation. A m ajor defect in the kakapo mutant tendon cells is the failure of Vein to be localized at the muscle-tendon junctional site; instead, Vein is dispersed and its levels are reduced. This may lead to aberrant differentiation of te ndon cells and consequently to the kakapo mutant deranged somatic muscle ph enotype.