Histogenesis of the cerebral cortex in rat fetuses with a mutation in the Pax-6 gene.
The embryonic development of the cerebral cortex was histologically examined in rat homozygotes with a mutation of the Paired box (Pax)-6 gene, rat Small eye (rSey(2)/rSey(2)). Although the cerebral wall was thinner in rSey(2)/rSey(2) than in the wild type at embryonic day 16 (E16), cortical cells of mutants labeled with 5'-bromodeoxyuridine (BrdU) at E13 migrated as normal, settling in superficial layer at E16. Mitotic activity in the ventricular zone, estimated by immunoreactivity for proliferating cell nuclear antigen (PCNA), was also retained. On the other hand, after E20 cells were clustered in abnormally expanded ventricular and intermediate zones of the rSey(2)/rSey(2) cortex. Birthdating studies using BrdU revealed that most of these clustered cells were generated between E18 and E20. Most of clustered cells were immunoreactive for PCNA and highly polysialylated NCAM, while immunoreaction for neurofilament and microtubule-associated protein-2 (MAP-2) was hardly detected in the clusters. Furthermore, apoptosis detected with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) was rarely seen, suggesting that the clustered cells remain in an undifferentiating state, but not degenerated by the end of the gestational period. Considering that Pax-6 immunoreactivity was exclusively localized in the ventricular zone of the normal rat cortex throughout the fetal period, the present results suggest that Pax-6 is crucial for differentiation and migration of late-generated cortical neurons.
Fukuda
T
T
Department of Anatomy, School of Medicine, Keio University, Tokyo, Japan.
Kawano
H
H
Osumi
N
N
Eto
K
K
Kawamura
K
K
D000818:Animals; D000963:Antimetabolites; D017209:Apoptosis / Q000235:genetics*; D001973:Bromodeoxyuridine; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000196:embryology*; D053938:DNA Fragmentation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005124:Eye Abnormalities / Q000235:genetics; D005136:Eye Proteins; D018398:Homeodomain Proteins; D006720:Homozygote; D020287:In Situ Nick-End Labeling; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009154:Mutation; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules / Q000032:analysis / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000502:physiology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins; D012794:Sialic Acids / Q000032:analysis / Q000378:metabolism
D000963:Antimetabolites; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D008869:Microtubule-Associated Proteins; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605733:Pax6 protein, rat; D018809:Proliferating Cell Nuclear Antigen; D012097:Repressor Proteins; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D001973:Bromodeoxyuridine