The Drosophila blood brain barrier is maintained by GPCR-dependent dynamic actin structures

Area of Science:

• Neuroscience
• Cell Biology
• Developmental Biology

Background:

• The blood-brain barrier (BBB) insulates the nervous system.
• In Drosophila, the BBB relies on septate junctions between subperineurial glia (SPG).
• The Moody/G protein-coupled receptor (GPCR) pathway is essential for BBB maintenance.

Purpose of the Study:

• To identify novel structures involved in Drosophila BBB maintenance.
• To elucidate the role of Moody/GPCR signaling in BBB formation.
• To investigate the mechanism of BBB sealing during development.

Main Methods:

• Live imaging of subperineurial glia (SPG) in Drosophila.
• Analysis of actin-rich structures (ARSs) and nonmuscle myosin localization.
• Genetic manipulation of the Moody/GPCR pathway and actin regulators (Arp2/3 complex).
• Measurement of intracellular calcium (Ca2+) levels and myosin light chain phosphorylation.

Main Results:

• Discovery of specialized actin-rich structures (ARSs) along SPG lateral borders.
• ARS formation is regulated by Moody/GPCR signaling and requires myosin activation.
• ARS localization correlates with elevated Ca2+ and myosin light chain phosphorylation.
• Inhibition of Arp2/3 complex disrupts ARSs and abrogates the BBB.
• ARSs are positioned near septate junctions for efficient sealing.

Conclusions:

• Moody/GPCR-dependent ARS formation, supported by myosin activation, maintains the Drosophila BBB.
• ARSs play a critical role in sealing membrane gaps during nerve cord growth.
• This study reveals a novel mechanism for BBB integrity in Drosophila.