Notch-, Wingless-, and Dpp-mediated signaling pathways are required for functional specification of Drosophila midgut cells

The mechanisms for cell fate determination have been extensively studied whereas little is known about the mechanism through which functional specificity is established. In the Drosophila midgut, copper cells provide an excellent model system to examine this mechanism. Copper is an essential element for the activity of a number of physiologically important enzymes including Cu/Zn-superoxide dismutase, cytochrome c oxidase, and dopamine-β-hydroxylase. Drosophila copper cells are involved in two distinct functions, i.e., copper absorption and acid secretion, which are visualized as a fluorescent signal and a color change of a pH indicator dye, respectively. Here we show that the absorptive function is established through two independent pathways, the Notch signaling pathway in adjacent interstitial cells and the Wingless signaling pathway in copper cells. Furthermore, the other function, acid secretion, is regulated through the Decapentaplegic and Wingless signaling pathways in interstitial cells. Our results clearly indicate that normal morphological development is insufficient for functional maturation, and that subsequent functional specification is achieved through several independent pathways. These results provide valuable insights into the molecular mechanism underlying functional specification.