Single-Cell Analysis of Rohon-Beard Neurons Implicates Fgf Signaling in Axon Maintenance and Cell Survival

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Peripheral sensory neurons transmit sensory information to the central nervous system.
• Rohon-Beard (RB) somatosensory neurons in zebrafish mediate this function during larval stages.
• Previous research suggested RB heterogeneity, but subtypes remained undefined.

Purpose of the Study:

• To molecularly define the subtypes of larval zebrafish RB neurons.
• To investigate the role of the fibroblast growth factor (Fgf) pathway in RB neuron maintenance.
• To explore therapeutic strategies against drug-induced peripheral neuropathy.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) to profile larval RB neurons.
• Cross-species transcriptional analysis to compare RB subclasses with mammalian neurons.
• Pharmacological and genetic inhibition of the Fgf pathway; assessment of axon integrity and cell death; Sarm1 manipulation.

Main Results:

• Larval RBs comprise three distinct, largely nonoverlapping molecular classes, differing from trigeminal neurons.
• One RB subclass shows similarity to mammalian A-fiber sensory neurons; another is predicted to sense mechanical and chemical stimuli.
• Fgf pathway activation is essential for RB axon maintenance and survival; Fgf inhibition (e.g., dovitinib) causes axon loss, which is Sarm1-dependent.

Conclusions:

• Zebrafish larval RBs are molecularly diverse, falling into three distinct subtypes.
• The Fgf pathway is critical for RB neuron integrity, and its inhibition can lead to peripheral neuropathy.
• Targeting Sarm1 may offer a strategy to mitigate dovitinib-induced neurotoxicity.