Neurons tend to stop migration and differentiate along the cortical internal plexiform zones in the Reelin signal-deficient mice.
The Reelin molecule plays a fundamental role in corticogenesis. After Reelin binds to its receptors, the Reelin signal is transduced through tyrosine phosphorylation of the intracellular adaptor protein disabled 1 (Dab1). The reelin-gene-deficient mouse, reeler, and Dab1-deficient mouse, yotari, show disrupted positioning of neurons. Several molecules have been identified recently as being involved in Reelin signaling, however, the biological function of Reelin during cortical plate development was still unknown. We observed the migrating behavior of neurons during development in Reelin-signal-deficient mice. To visualize the migrating neurons directly, we introduced green fluorescent protein (GFP)-expression vectors into the ventricular zone with an in utero electroporation system and allowed the embryos to develop in utero until they were analyzed. The result showed that the migrating cells in the mutants were morphologically indistinguishable from those of normal mice. At the stage when the GFP-expressing cells reached the marginal zone near the pial surface and began dendrite formation in normal mice, the GFP-positive cells were found at various deeper positions in the mutant cortex. They had the morphology of migrating cells extending leading processes toward the pial surface. By contrast, in the mutants these cells tended to stop migration along the borders of the internal plexiform zone, the irregular structure consisting mainly of dendrites in the mutant cortex. Postnatally, these neurons began to develop dendrites later than the cells in the normal cortex. During this process, some neurons above the internal plexiform zone extended and developed dendrites in the opposite direction into the internal plexiform zone. These results suggest that the abnormal positioning of neurons in the Reelin-signal-deficient mice is caused, at least in part, by abnormal formation of the internal plexiform zone in the mutant cortex.
Tabata
Hidenori
H
Department of Molecular Neurobiology, Institute of DNA Medicine, Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
Nakajima
Kazunori
K
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology*; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D015398:Signal Transduction / Q000502:physiology
D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D049452:Green Fluorescent Proteins; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases