Glial TGFβ activity promotes neuron survival in peripheral nerves

Alexandria P. Lassetter, Megan M. Corty, Romina Barria, Amy E. Sheehan, Jo Q. Hill, Sue A. Aicher, A. Nicole Fox, Marc R. Freeman

Research output: Contribution to journalArticlepeer-review

Abstract

Maintaining long, energetically demanding axons throughout the life of an animal is a major challenge for the nervous system. Specialized glia ensheathe axons and support their function and integrity throughout life, but glial support mechanisms remain poorly defined. Here, we identified a collection of secreted and transmembrane molecules required in glia for long-term axon survival in vivo. We showed that the majority of components of the TGFβ superfamily are required in glia for sensory neuron maintenance but not glial ensheathment of axons. In the absence of glial TGFβ signaling, neurons undergo age-dependent degeneration that can be rescued either by genetic blockade of Wallerian degeneration or caspase-dependent death. Blockade of glial TGFβ signaling results in increased ATP in glia that can be mimicked by enhancing glial mitochondrial biogenesis or suppressing glial monocarboxylate transporter function. We propose that glial TGFβ signaling supports axon survival and suppresses neurodegeneration through promoting glial metabolic support of neurons.

Original languageEnglish (US)
Article numbere202111053
JournalJournal of Cell Biology
Volume222
Issue number1
DOIs
StatePublished - Jan 2 2023
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

Fingerprint

Dive into the research topics of 'Glial TGFβ activity promotes neuron survival in peripheral nerves'. Together they form a unique fingerprint.

Cite this