Merkel Cell-Driven BDNF Signaling Specifies SAI Neuron Molecular and Electrophysiological Phenotypes

Area of Science:

• Neuroscience
• Developmental Biology
• Dermatology

Background:

• Peripheral sensory neuron diversity arises from intrinsic and local factors.
• The role of target tissues in sensory neuron development is largely unknown.
• Merkel cells are specialized skin cells innervated by sensory neurons.

Purpose of the Study:

• To investigate if skin cells, specifically Merkel cells, instruct peripheral somatosensory neuron maturation.
• To elucidate the molecular mechanisms by which Merkel cells influence sensory neuron development.

Main Methods:

• Utilized transgenic mice lacking Merkel cells.
• Examined gene and protein expression in dorsal root ganglion (DRG) neurons.
• Performed genetic deletion of specific genes (Bdnf, Ntf3) in Merkel cells during embryogenesis.
• Assessed electrophysiological properties of sensory neurons.

Main Results:

• Mice lacking Merkel cells showed altered expression of key sensory neuron markers (TrkB, TrkC, Ret) and downstream signaling.
• Embryonic deletion of Brain-Derived Neurotrophic Factor (BDNF) in Merkel cells phenocopied the effects of Merkel cell ablation.
• Postnatal deletion of BDNF or deletion of Neurotrophin-3 (Ntf3) did not yield the same results.
• Sensory neurons lacked specific electrophysiological signatures when BDNF was deleted in embryonic Merkel cells.

Conclusions:

• Merkel cells are essential for the molecular and functional maturation of innervating slowly adapting type I (SAI) neurons.
• BDNF signaling from Merkel cells during a critical embryonic window directs SAI neuron development.
• This study provides the first direct evidence of skin-derived factors instructing sensory neuron maturation and reveals a novel role for Merkel cells in mechanosensation.