Autonomic and Peripheral Nerve Development

Autonomic and peripheral nerve development is the building of the nervous system outside the brain and spinal cord. Most of it derives from the neural crest: sensory neurons of the dorsal root and cranial ganglia, the sympathetic, parasympathetic, and enteric autonomic neurons, and the Schwann cells that ensheath peripheral axons, together with motor axons that grow out of the central nervous system to reach their targets.

Definition

Autonomic and peripheral nerve development is the process by which neural-crest-derived cells form the peripheral sensory ganglia and the sympathetic, parasympathetic, and enteric divisions of the autonomic nervous system, along with peripheral glia, while central motor and sensory axons connect with these peripheral elements.

Scope

The entry covers the neural-crest origin of peripheral sensory and autonomic neurons, the formation of dorsal root, sympathetic, parasympathetic, and enteric ganglia, the development of Schwann cells, and the outgrowth and guidance of peripheral axons. It is an educational reference to developmental anatomy, not clinical guidance.

Key concepts

• Neural-crest origin of peripheral neurons
• Dorsal root and cranial sensory ganglia
• Sympathetic and parasympathetic ganglia
• Enteric nervous system
• Schwann cell precursors
• Neurotrophic signalling
• Axon guidance and target innervation
• Sensory and autonomic neuron specification

Mechanisms

Trunk neural crest cells migrating ventrally aggregate to form dorsal root sensory ganglia and the sympathetic chain, where local and systemic signals specify sensory versus autonomic identity and drive differentiation. Vagal and sacral crest colonize the gut wall to establish the enteric nervous system, the largest division of the autonomic nervous system. Schwann cell precursors, themselves of neural crest origin, accompany growing nerves and have been shown to contribute neurons to some parasympathetic ganglia. Neurons depend on neurotrophic factors supplied by their targets for survival and for the matching of neuron number to target size, and their axons are guided to appropriate destinations by attractive and repulsive cues. Centrally derived motor axons grow out to muscle while peripheral sensory axons project both centrally and peripherally, wiring the peripheral nervous system into the central nervous system.

Clinical relevance

Failure of vagal and sacral crest cells to fully colonize the gut leaves a segment without enteric ganglia, the developmental basis of congenital aganglionic megacolon (Hirschsprung disease), and disorders of peripheral neuron or Schwann cell development affect sensation and autonomic function. This entry describes the underlying developmental biology for reference and education and is not a basis for individual diagnosis or treatment.

History

Experimental embryology established that peripheral sensory and autonomic neurons and peripheral glia originate from the neural crest, and the neurotrophic hypothesis explained how target-derived factors regulate neuronal survival. More recent lineage studies have refined origins further, for example evidence that some parasympathetic neurons derive from nerve-associated Schwann cell precursors.

Debates

What is the origin of parasympathetic neurons?

Parasympathetic neurons were traditionally attributed to crest cells migrating directly to ganglia, but lineage-tracing evidence indicates that many derive from Schwann cell precursors associated with peripheral nerves, prompting reassessment of autonomic origins.

Key figures

• Patrik Ernfors
• John B. Furness
• Jean-François Brunet

Seminal works

• marmigere-2007
• furness-2012
• espinosa-medina-2014

Frequently asked questions

Where do peripheral and autonomic neurons come from?

Most peripheral sensory and autonomic neurons and the Schwann cells that support peripheral axons derive from the neural crest, a migratory cell population that leaves the dorsal neural tube.

What is the enteric nervous system and where does it come from?

It is the extensive network of neurons within the gut wall, the largest division of the autonomic nervous system, and it is formed mainly by vagal and sacral neural crest cells that colonize the developing intestine.