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Cerebral Cortex Advance Access originally published online on October 26, 2007
Cerebral Cortex 2008 18(7):1536-1548; doi:10.1093/cercor/bhm184
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© 2007 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

A Molecular Neuroanatomical Study of the Developing Human Neocortex from 8 to 17 Postconceptional Weeks Revealing the Early Differentiation of the Subplate and Subventricular Zone

Nadhim Bayatti1, Jennifer A. Moss1, Li Sun2, Philip Ambrose1, Joseph F. H. Ward1, Susan Lindsay1,3 and Gavin J. Clowry1

1 School of Clinical Medical Sciences, Department of Child Health, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK, 2 School of Biology and Psychology, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK, 3 Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK

Address correspondence to Dr Gavin Clowry, Sir James Spence Institute for Child Health, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK. Email: g.j.clowry{at}ncl.ac.uk.

We have employed immunohistochemistry for multiple markers to investigate the structure and possible function of the different compartments of human cerebral wall from the formation of cortical plate at 8 postconceptional weeks (PCW) to the arrival of thalamocortical afferents at 17 PCW. New observations include the subplate emerging as a discrete differentiated layer by 10 PCW, characterized by synaptophysin and vesicular gamma-aminobutyric acid transporter expression also seen in the marginal zone, suggesting that these compartments may maintain a spontaneously active synaptic network even before the arrival of thalamocortical afferents. The subplate expanded from 13 to 17 PCW, becoming the largest compartment and differentiated further, with NPY neurons located in the outer subplate and KCC2 neurons in the inner subplate. Glutamate decarboxylase and calretinin-positive inhibitory neurons migrated tangentially and radially from 11.5 PCW, appearing in larger numbers toward the rostral pole. The proliferative zones, marked by Ki67 expression, developed a complicated structure by 12.5 PCW reflected in transcription factor expression patterns, including TBR2 confined to the inner subventricular and outer ventricular zones and TBR1 weakly expressed in the subventricular zone (SVZ). PAX6 was extensively expressed in the proliferative zones such that the human outer SVZ contained a large reservoir of PAX6-positive potential progenitor cells.

Key Words: cell migration • cortical development • immunohistochemistry • synaptogenesis


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