Figure 2. Seamless tube formation and growth in the Drosophila tracheal system.
(A) Developmental timeline for one dorsal branch [6] and roles of FGF and Wnt signaling. Heavy black lines represent junctions. FGF signaling promotes tip cell identity (gray) [31] and expression or activity of Singed/Fascin [37], Mipp 1 and 2 [34], and Rac [36], which promote filopodia maturation leading to tip cell migration and outgrowth. The FGFR target Pointed (Pnt) promotes terminal cell identity (pink) [6, 31] and expression of the DSRF transcription factor for tube morphogenesis [106]. DSRF upregulates Enabled (Ena) to promote actin filament elongation [35]. Wnt signaling promotes Escargot (Esc) expression and fusion cell identity (purple) [33]. Fusion cells express the transcription factor Dysfusion (Dys) and upregulate Deadend (Dnd)/Arl3 and Shotgun/E-cadherin to promote anastomosis [71, 72, 107, 108]. The terminal cell turns ventrally and builds lumen starting at the stalk cell interface [35]. The fusion cell extends filopodia dorsally in search of its partner fusion cell [28]. (B) Structure and organization of a growing terminal cell. Multivesicular bodies are present near the leading edge at later stages [55]. Actin is found along the apical and basal membranes and at the leading edge [35, 79]. Microtubules are nucleated along the apical membrane, and extend toward the leading edge [35, 50, 94]. The (−) end directed MT motor dynamin is required for lumen growth [50]. Moesin organizes actin at the apical membrane [80]. Integrins link the basal cell membrane to the basal ECM [45]. (C) Model for terminal cell apical domain organization. Bitesize and Crumbs recruit Moesin to the apical membrane [53, 80], where it is phosphorylated and activated by Slik [38]. Moesin then recruits actin to promote apical-directed trafficking. PAR proteins recruit the exocyst complex for vesicle docking [48]. A chitin rod determines lumen diameter [86, 87, 97, 98]. The ZP proteins Dumpy (Dpy) and Piopio (Pio) may link the chitin rod to the apical membrane and cytoskeleton [60, 93–95].