TrkB regulates neocortex formation through the Shc/PLCgamma-mediated control of neuronal migration.
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 Cgamma (PLCgamma), 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 PLCgamma.
Medina
Diego L
DL
European Molecular Biology Laboratory, Monterotondo, Italy.
Sciarretta
Carla
C
Calella
Anna Maria
AM
Von Bohlen Und Halbach
Oliver
O
Unsicker
Klaus
K
Minichiello
Liliana
L
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D019426:Integrases; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis; D009186:Myelin Sheath / Q000378:metabolism; D019579:Neocortex / Q000196:embryology* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism; D051966:Phospholipase C gamma; D020813:Receptor, trkB / Q000235:genetics / Q000502:physiology*; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D010738:Type C Phospholipases / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D020813:Receptor, trkB; C045073:Cre recombinase; D019426:Integrases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D001973:Bromodeoxyuridine