Neuronal Nogo-A regulates neurite fasciculation, branching and extension in the developing nervous system.
Wiring of the nervous system is a multi-step process involving complex interactions of the growing fibre with its tissue environment and with neighbouring fibres. Nogo-A is a membrane protein enriched in the adult central nervous system (CNS) myelin, where it restricts the capacity of axons to grow and regenerate after injury. During development, Nogo-A is also expressed by neurons but its function in this cell type is poorly known. Here, we show that neutralization of neuronal Nogo-A or Nogo-A gene ablation (KO) leads to longer neurites, increased fasciculation, and decreased branching of cultured dorsal root ganglion neurons. The same effects are seen with antibodies against the Nogo receptor complex components NgR and Lingo1, or by blocking the downstream effector Rho kinase (ROCK). In the chicken embryo, in ovo injection of anti-Nogo-A antibodies leads to aberrant innervation of the hindlimb. Genetic ablation of Nogo-A causes increased fasciculation and reduced branching of peripheral nerves in Nogo-A KO mouse embryos. Thus, Nogo-A is a developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching.
Petrinovic
Marija M
MM
Brain Research Institute, University of Zurich and Department of Biology, ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. petrinovic@hifo.uzh.ch
Duncan
Carri S
CS
Bourikas
Dimitris
D
Weinman
Oliver
O
Montani
Laura
L
Schroeter
Aileen
A
Maerki
David
D
Sommer
Lukas
L
Stoeckli
Esther T
ET
Schwab
Martin E
ME
D000818:Animals; D001369:Axons / Q000378:metabolism; D002642:Chick Embryo; D005727:Ganglia, Spinal / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009185:Myelin Proteins / Q000378:metabolism*; D009420:Nervous System; D009474:Neurons / Q000378:metabolism*; D000070798:Nogo Proteins; D051381:Rats; D017208:Rats, Wistar; D011995:Recombination, Genetic; D054460:rho-Associated Kinases / Q000378:metabolism
D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat; D054460:rho-Associated Kinases