Septate junction formation and maintenance in the invertebrate BBB. Components of the core septate junction (green) and the associated proteins that maintain BBB integrity (black) were identified from loss of function mutants that led to a porous BBB phenotype. Discs large (Dlg) mutants showed delayed assembly of the core septate junction components, whereas mutants of Gliotactin, and the endocytic proteins Clathrin-heavy chain (Chc) and Shibire, showed a mislocalization of the septate junction core. The Moody GPCR signaling pathway (Moody, Gαo/Gαi, loco) was shown to genetically interact with actin and non-muscle myosin components [actin-rich structures (ARS), Zipper, Spaghetti squash (Sqh)] to maintain septate junction integrity. Kinesin heavy chain (Khc) may regulate septate junction integrity by transporting Neurexin IV as a cargo protein. Loss of septate junction integrity by disrupting the function of wunen, the lipid phosphate phosphatase, suggests a role for bioactive lipids in paracellular barrier function. NL, neural lamella; PG, perineurial glia; SPG, subperineurial glia; CNS, central nervous system; kune (kune-kune).