Neuronal pathfinding is abnormal in mice lacking the neuronal growth cone protein GAP-43.
GAP-43 has been termed a "growth" or "plasticity" protein because it is expressed at high levels in neuronal growth cones during development and during axonal regeneration. By homologous recombination, we generated mice lacking GAP-43. The mice die in the early postnatal period. GAP-43-deficient retinal axons remain trapped in the chiasm for 6 days, unable to navigate past this midline decision point. Over the subsequent weeks of life, most GAP-43-deficient axons do enter the appropriate tracts, and the adult CNS is grossly normal. There is no evidence for interference with nerve growth rate, and cultured neurons extend neurites and growth cones in a fashion indistinguishable from controls. Thus, the GAP-43 protein is not essential for axonal outgrowth or growth cone formation per se, but is required at certain decision points, such as the optic chiasm. This is compatible with the hypothesis that GAP-43 serves to amplify pathfinding signals from the growth cone.
Developmental Biology Laboratory, Harvard Medical School, Massachusetts General Hospital-East, Charlestown 02129.
S M
SM
Strittmatter
C
C
Fankhauser
P L
PL
Huang
H
H
Mashimo
M C
MC
Fishman
D000818:Animals; D001369:Axons / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002678:Chimera; D005260:Female; D019922:GAP-43 Protein; D005727:Ganglia, Spinal / Q000166:cytology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009897:Optic Chiasm / Q000166:cytology / Q000196:embryology*; D011995:Recombination, Genetic; D012160:Retina / Q000196:embryology*; D012165:Retinal Ganglion Cells / Q000166:cytology; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D014276:Trigeminal Nerve / Q000196:embryology / Q000502:physiology
D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins