Cerebral Cortex Advance Access originally published online on July 6, 2005
Cerebral Cortex 2006 16(4):487-499; doi:10.1093/cercor/bhi128
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BDNF-modulated Spatial Organization of Cajal–Retzius and GABAergic Neurons in the Marginal Zone Plays a Role in the Development of Cortical Organization
1 Department of Cell Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain, 4 Institut de Recerca de Barcelona, Parc Cientific de Barcelona, Spain and 5 Division of Molecular Neurobiology, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden, 2 Present address: Department of Experimental Pathology and Therapeutics, School of Medicine, University of Barcelona, Spain, 3 Present address: Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Address correspondence to Soledad Alcántara, Department of Experimental Pathology and Therapeutics, School of Medicine, University of Barcelona, 08907 L'Hospitalet de Llobregat, Spain. Email: salcantara{at}ub.edu.
The present study utilizes nestin-BDNF transgenic mice, which offer a model for early increased brain-derived neurotrophic factor (BDNF) signalling, to examine the role of BDNF in the development of cortical architecture. Our results demonstrate that the premature and homogeneous expression of BDNF, while preserving tangential migration from the ganglionic eminence to the cortex, impairs the final radial migration of GABAergic neurons, as well as their integration in the appropriate cortical layers. Moreover, Cajal–Retzius (CR) cells and GABAergic neurons segregate in the cortical marginal zone (MZ) in response to BDNF signalling, leading to an alternating pattern and a columnar cortical organization, within which the migration of different neuronal populations is specifically affected. These results suggest that both CR and GABAergic neurons play a role in directing the radial migration of late-generated cortical neurons, and that the spatial distribution of these cells in the MZ is critical for the development of correct cortical organization. In addition, reelin secreted by CR cells in the MZ is not sufficient to direct the migration of late-born neurons to the upper cortical layers, which most likely requires the presence of reelin-secreting interneurons in layers V–VI. We propose that in addition to modulating reelin expression, BDNF regulates the patched distribution of CR and GABAergic neurons in the MZ, and that this spatial distribution is involved in the formation of anatomical and/or functional columns and convoluted structures.
Key Words: BDNF • Cajal-Retzius cells • cerebral cortex • GABAergic neurons • neuronal migration • reelin