Article
- The EMBO Journal (2004) 23, 3803 - 3814
- doi:10.1038/sj.emboj.7600399
Published online: 16 September 2004
Subject Categories:
TrkB regulates neocortex formation through the Shc/PLC
-mediated control of neuronal migration
Diego L Medina1, Carla Sciarretta1, Anna Maria Calella1, Oliver von Bohlen und Halbach2, Klaus Unsicker2 and Liliana Minichiello1
- European Molecular Biology Laboratory, Monterotondo, Italy
- Interdisciplinary Center for Neurosciences (IZN), Department of Neuroanatomy, University of Heidelberg, Heidelberg, Germany
Correspondence to:
Liliana Minichiello, EMBL, Mouse Biology Programme, via Ramarini 32, 00016 Monterotondo, Rome, Italy. Tel.: +39 06 90091 291; Fax: +39 06 90091 272; E-mail: minichiello@embl-monterotondo.it
Received 18 March 2004; Accepted 16 August 2004
Abstract
The generation of complex neuronal structures, such as the neocortex, requires accurate positioning of neurons and glia within the structure, followed by differentiation, formation of neuronal connections, and myelination. To understand the importance of TrkB signaling during these events, we have used conditional and knockin mutagenesis of the TrkB neurotrophin receptor, and we now show that this tyrosine kinase receptor, through docking sites for the Shc/FRS2 adaptors and phospholipase C
(PLC), coordinates these events in the cerebral cortex by (1) controlling cortical stratification through the timing of neuronal migration during cortex formation, and (2) regulating both neuronal and oligodendrocyte differentiation. These results provide genetic evidence that TrkB regulates important functions throughout the formation of the cerebral cortex via recruitment of the Shc/FRS2 adaptors and PLC.
Keywords:
- cell differentiation,
- cell migration,
- neocortex development,
- TrkB signaling
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