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Cerebral Cortex 2006 16(Supplement 1):i35-i45; doi:10.1093/cercor/bhj172
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Role of p35/Cdk5 in Preplate Splitting in the Developing Cerebral Cortex

Sonja Rakic1, Colin Davis1, Zoltán Molnár2, Margareta Nikolic3 and John G. Parnavelas1

1 Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, UK, 2 Department of Human Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK and 3 Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Imperial College Faculty of Medicine, London W6 8RP, UK

Address correspondence to John G. Parnavelas, Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK. Email: j.parnavelas{at}ucl.ac.uk.

The earliest generated cells of the mammalian cerebral cortex form the preplate layer (PPL). The subsequently born cortical plate (CP) cells split this layer into the superficial layer I (LI) and the deep subplate (SP). The cellular and molecular mechanisms that underlie this event are unclear. To investigate the role of the cyclin-dependent kinase 5 (Cdk5) and its activator p35 in preplate splitting, we used Nissl staining, carbocyanine dye tracing, cell birthdating, and immunohistochemistry for calretinin (CalR) in p35 and Cdk5 knockout mice. Our data demonstrated changes in early cortical lamination and aberrant thalamic axon trajectories in these mice. Specifically, LI was thicker, and cell-dense and thalamic axons did not accumulate in the SP layer before invading the CP. Instead, they grew past the SP and more superficial cortical layers and coursed obliquely toward the pial surface. This behavior has been previously observed in reeler mice and suggests a defect in PPL splitting. CalR immunohistochemistry and bromo-deoxyuridine birthdating confirmed the abnormality in position of the earliest generated cortical cells of mutants. These observations suggest that the p35/Cdk5 pathway plays a role in preplate splitting in addition to regulating layer formation.

Key Words: axons • development • layer I • subplate • thalamus


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