Jeb signals through the Alk receptor tyrosine kinase to drive visceral muscle fusion

The Drosophila melanogaster gene Anaplastic lymphoma kinase ( Alk ) is homologous to mammalian Alk, a member of the Alk/Ltk family of receptor tyrosine kinases (RTKs) 1 . We have previously shown that the Drosophila Alk RTK is crucial for visceral mesoderm development during early embryogenesis 2 . Notably, observed Alk visceral mesoderm defects are highly reminiscent of the phenotype reported for the secreted molecule Jelly belly (Jeb) 3 . Here we show that Drosophila Alk is the receptor for Jeb in the developing visceral mesoderm, and that Jeb binding stimulates an Alk-driven, extracellular signal-regulated kinase-mediated signalling pathway, which results in the expression of the downstream gene duf (also known as kirre ) 4 , 5 —needed for muscle fusion. This new signal transduction pathway drives specification of the muscle founder cells, and the regulation of Duf expression by the Drosophila Alk RTK explains the visceral-mesoderm-specific muscle fusion defects observed in both Alk and jeb mutant animals.