Control of neuron shape during development and regeneration

Abstract

We have examined the ability of Mueller reticulospinal neurons in the CNS of the larval sea lamprey to sprout following axonal and dendritic injury. Axotomy induces regenerative sprouting exclusively from the axon stump if it occurs at a site distant from the soma in the spinal cord. However, axotomy within the hindbrain at a site close to the soma results in profuse neuritic sprouting from the dendrites. The gross morphology and trajectories of these "dendritic" sprouts resemble those of regenerating axons. Amputation of Mueller cell dendrites (dendrotomy) without axotomy does not result in neuritic sprouting from either the axon or dendrites, indicating that axotomy is specifically required for sprouting to occur. However, dendrotomy is capable of altering the distribution of sprouting in a previously axotomized Mueller cell by inducing sprouting at the site of the dendrotomy lesion. Sprouts of both dendritic and axonal origin tend to follow linear, rostrocaudally oriented paths along or near the ventral surface of the hindbrain. Some sprouts form very large, palmate growth cones on the marginal surface, which in turn give rise to many branches that continue to grow either rostrally or caudally along the surface of the brain. We discuss the possibility that both dendritic and axonal sprouts evoked by axotomy of Mueller neurons are recapitulating initial axonal development during embryogenesis, and that their trajectories are determined by developmental guidance cues persisting in the ventral hindbrain.