Effects of L1 blockade on sensory axon outgrowth and pathfinding in the chick hindlimb.
In the developing chick hindlimb, sensory axons, which grow together in bundles as they extend distally, and the motoneuron axons they encounter express the cell adhesion molecule L1. Following injection of function-blocking anti-L1 antibodies into the limb at stage 25, some sensory axons choose inappropriate peripheral nerves even though motoneuron pathfinding is unaffected. Here, to further elucidate L1's role, we assessed the effects of this perturbation using pathway tracing, immune labeling, confocal microscopy, and electron microscopy. After L1 blockade, sensory axons were still bundled and closely apposed. However, clear signs of decreased adhesion were detectable ultrastructurally. Further, sensory axons grew into the limb more slowly than normal, wandering more widely, branching more frequently, and sometimes extending along inappropriate peripheral nerves. Sensory axons that ultimately projected along different cutaneous nerves showed increased intermixing in the spinal nerves, due to errors in pathfinding and also to a decreased ability to segregate into nerve-specific fascicles. These results suggest that, in the highly complex in vivo environment, as in tissue culture, L1 stimulates axon growth and enhances fasciculation, and that these processes contribute to the orderly, timely, and specific growth of sensory axons into the limb.
Honig
Marcia G
MG
Department of Anatomy and Neurobiology, University of Tennessee College of Medicine, The Health Science Center, Memphis, Tennessee 38163, USA. mhonig@utmem.edu
Camilli
Suzanne J
SJ
Xue
Qing-Shan
QS
D000818:Animals; D000911:Antibodies, Monoclonal; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000502:physiology; D002642:Chick Embryo; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D006614:Hindlimb / Q000166:cytology* / Q000196:embryology / Q000502:physiology; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000502:physiology*; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D019006:Neural Cell Adhesion Molecules / Q000502:physiology*
D000911:Antibodies, Monoclonal; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules