Journal
DEVELOPMENTAL BRAIN RESEARCH
Volume 120, Issue 1, Pages 65-75Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0165-3806(99)00187-X
Keywords
rat Small eye (rSey); Pax-6; 5 '-bromodeoxyuridine (BrdU); terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL); highly polysialylated NCAM (PSA-NCAM); cerebral cortex
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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)/Sey(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)/eSey(2) cortex. Birthdating studies using BrdU revealed that most of these clustered cells were generated between Els 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. (C) 2000 Elsevier Science B.V. All rights reserved.
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