Callosal axon guidance defects in p35(-/-) mice.
Mice lacking p35, an activator of cdk5 in the central nervous system (CNS), exhibit defects in a variety of CNS structures, most prominently characterized by a disruption in the laminar structure of the neocortex (Chae et al., 1997). In addition, alterations of certain axonal fiber tracts are found in the cortex of p35 mutant mice. Notably, the corpus callosum appears bundled at the midline, but dispersed lateral to the midline. Tracer injection experiments in adult p35 mutant mice reveal that projecting cortical axons fail to assimilate into the corpus callosum, and take oblique paths to the midline. After crossing the midline, cortical axons defasciculate prematurely from the corpus callosum and take similarly oblique paths through the cortex. This callosal phenotype is not detected in reeler mice, which also exhibit defects in cortical lamination, suggesting that the lack of fasciculation of callosal axons is not an inherent manifestation of a disruption of cortical lamination. The embryonic callosal axon tract is defasciculated before crossing the midline, suggesting that axon guidance may be affected during embryonic development of the corpus callosum. In addition, embryonic thalamocortical afferents also exhibit a defasciculated phenotype. These results suggest that defective axonal fasciculation and guidance may be primary responses to the loss of p35 in the cortex. Furthermore, this study postulates a role for the p35/cdk5 kinase in molecular signaling pathways necessary for proper guidance of selective axons during embryonic development.
Kwon
Y T
YT
Howard Hughes Medical Institute, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Tsai
L H
LH
Crandall
J E
JE
D061085:Agenesis of Corpus Callosum; D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics*; D002232:Carbocyanines; D003337:Corpus Callosum / Q000166:cytology*; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000502:physiology; D007150:Immunohistochemistry; D008074:Lipoproteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout / Q000002:abnormalities*; D008817:Mice, Mutant Strains / Q000002:abnormalities; D008818:Mice, Neurologic Mutants / Q000002:abnormalities; D009434:Neural Pathways / Q000002:abnormalities / Q000166:cytology; D010770:Phosphotransferases; D013003:Somatosensory Cortex / Q000002:abnormalities / Q000166:cytology; D013788:Thalamus / Q000002:abnormalities / Q000166:cytology
C035005:3,3'-dihexadecylindocarbocyanine; D001425:Bacterial Outer Membrane Proteins; D002232:Carbocyanines; C492236:Cdk5r1 protein, mouse; D008074:Lipoproteins; D010770:Phosphotransferases; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases