Related Experiment Video
Updated: Apr 21, 2026

Author Spotlight: Unveiling the Molecular Basis of Pain Perception and Neuropathic Pain
Published on: August 9, 2024
PI3K signaling and Stat92E converge to modulate glial responsiveness to axonal injury
Johnna Doherty1, Amy E Sheehan1, Rachel Bradshaw1
1Department of Neurobiology, Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Abstract:
Glial cells are exquisitely sensitive to neuronal injury but mechanisms by which glia establish competence to respond to injury, continuously gauge neuronal health, and rapidly activate reactive responses remain poorly defined. Here, we show glial PI3K signaling in the uninjured brain regulates baseline levels of Draper, a receptor essential for Drosophila glia to sense and respond to axonal injury. After injury, Draper levels are up-regulated through a Stat92E-modulated, injury-responsive enhancer element within the draper gene. Surprisingly, canonical JAK/STAT signaling does not regulate draper expression. Rather, we find injury-induced draper activation is downstream of the Draper/Src42a/Shark/Rac1 engulfment signaling pathway. Thus, PI3K signaling and Stat92E are critical in vivo regulators of glial responsiveness to axonal injury. We provide evidence for a positive auto-regulatory mechanism whereby signaling through the injury-responsive Draper receptor leads to Stat92E-dependent, transcriptional activation of the draper gene. We propose that Drosophila glia use this auto-regulatory loop as a mechanism to adjust their reactive state following injury.
Related Concept Videos
PI3K/mTOR/AKT Signaling Pathway
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
The JAK-STAT Signaling Pathway
Intracellular Signaling Affects Focal Adhesions
Some...
Amplifying Signals via Enzymatic Cascade
Neurogenesis and Regeneration of Nervous Tissue

