The Drosophila Blood-Brain Barrier Adapts to Cell Growth by Unfolding of Pre-existing Septate Junctions

The blood-brain barrier is crucial for nervous system function. It is established early during development and stays intact during growth of the brain. In invertebrates, septate junctions are the occluding junctions of this barrier. Here, we used Drosophila to address how septate junctions grow during larval stages when brain size increases dramatically. We show that septate junctions are preassembled as long, highly folded strands during embryonic stages, connecting cell vertices. During subsequent cell growth, these corrugated strands are stretched out and stay intact during larval life with very little protein turnover. The G-protein coupled receptor Moody orchestrates the continuous organization of junctional strands in a process requiring F-actin. Consequently, in moody mutants, septate junction strands cannot properly stretch out during cell growth. To compensate for the loss of blood-brain barrier function, moody mutants form interdigitating cell-cell protrusions, resembling the evolutionary ancient barrier type found in primitive vertebrates or invertebrates such as cuttlefish. [Display omitted] •Septate junction (SJ) proteins are stable for days•SJ strands are prefigured during embryogenesis and are unfolded during larval stages•The G-protein coupled receptor Moody suppresses interdigitating cell-cell protrusions•Moody promotes formation of continuous SJ strands Babatz et al. found that during Drosophila embryogenesis, the GPCR Moody promotes assembly of long, highly folded septate junction strands that are stretched out during larval life with little protein turnover. Loss of Moody results in an evolutionary ancient blood-brain barrier type comprising interdigitating glia as in primitive vertebrates and invertebrates.