Ectopic expression of the neural cell adhesion molecule L1 in astrocytes leads to changes in the development of the corticospinal tract.
The cell recognition molecule L1, of the immunoglobulin superfamily, participates in the formation of the nervous system and has been shown to enhance cell migration and neurite outgrowth in vitro. To test whether ectopic expression of L1 would influence axonal outgrowth in vivo, we studied the development of the corticospinal tract in transgenic mice expressing L1 in astrocytes under the control of the GFAP-promoter. Corticospinal axons innervate their targets by extending collateral branches interstitially along the axon shaft following a precise spatio-temporal pattern. Using DiI as an anterograde tracer, we found that in the transgenic animals, corticospinal axons appear to be defasciculated, reach their targets sooner and form collateral branches innervating the basilar pons at earlier developmental stages and more diffusely than in wild type littermates. Collateral branches in the transgenic mice did not start out as distinct rostral and caudal sets, but they branched from the axon segments in a continuous rostrocaudal direction across the entire region of the corticospinal tract overlying the basilar pons. The ectopic branches are transient and no longer present at postnatal day 22. The earlier outgrowth and altered branching pattern of corticospinal axons in the transgenics is accompanied by an earlier differentiation of astrocytes. Taken together, our observations provide evidence that the ectopic expression of L1 on astrocytes causes an earlier differentiation of these cells, results in faster progression of corticospinal axons and influences the branching pattern of corticospinal axons innervating the basilar pons.
Ourednik
J
J
Department of Neurobiology, Swiss Federal Institute of Technology, Hönggerberg, CH-8093 Zürich, Switzerland. jouredni@caregroup.harvard.edu
Ourednik
V
V
Bastmeyer
M
M
Schachner
M
M
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001973:Bromodeoxyuridine; D002232:Carbocyanines; D002454:Cell Differentiation / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D005333:Fetus; D005456:Fluorescent Dyes; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005838:Genotype; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D007150:Immunohistochemistry; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D011149:Pons / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D011401:Promoter Regions, Genetic / Q000235:genetics; D011712:Pyramidal Tracts / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D013003:Somatosensory Cortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D020651:Ventral Thalamic Nuclei / Q000166:cytology / Q000196:embryology / Q000254:growth & development
C035005:3,3'-dihexadecylindocarbocyanine; D002232:Carbocyanines; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D001973:Bromodeoxyuridine