In vivo evidence for transdifferentiation of peripheral neurons.
It is commonly thought that differentiated neurons do not give rise to new cells, severely limiting the potential for regeneration and repair of the mature nervous system. However, we have identified cells in zebrafish larvae that first differentiate into dorsal root ganglia sensory neurons but later acquire a sympathetic neuron phenotype. These transdifferentiating neurons are present in wild-type zebrafish. However, they are increased in number in larvae that have a mutant voltage-gated sodium channel gene, scn8aa. Sodium channel knock-down promotes migration of differentiated sensory neurons away from the ganglia. Once in a new environment, sensory neurons transdifferentiate regardless of sodium channel expression. These findings reveal an unsuspected plasticity in differentiated neurons that points to new strategies for treatment of nervous system disease.
Wright
Melissa A
MA
Department of Physiology and Biophysics, Neuroscience Graduate Program and Medical Scientist Training Program, Anschutz Medical Campus, University of Colorado, 12800 East 19th Avenue, Mail Stop 8307, PO Box 6511, Aurora, CO 80045, USA. melissa.wright@ucdenver.edu
Mo
Weike
W
Nicolson
Teresa
T
Ribera
Angeles B
AB
D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation; D002465:Cell Movement; D054338:Cell Transdifferentiation; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D009154:Mutation; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D015222:Sodium Channels / Q000172:deficiency / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015027:Zebrafish / Q000254:growth & development* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000172:deficiency / Q000378:metabolism*
D062557:NAV1.6 Voltage-Gated Sodium Channel; D015222:Sodium Channels; D029961:Zebrafish Proteins; C515010:scn8aa protein, zebrafish; D014446:Tyrosine 3-Monooxygenase