TY - JOUR
T1 - Reelin Regulates Cadherin Function via Dab1/Rap1 to Control Neuronal Migration and Lamination in the Neocortex
AU - Franco, Santos J.
AU - Martinez-Garay, Isabel
AU - Gil-Sanz, Cristina
AU - Harkins-Perry, Sarah R.
AU - Müller, Ulrich
N1 - Funding Information:
We thank G. Bokoch, J. Cooper, M. Ginsberg, and S. Halpain for reagents; K. Spencer and M. Wood for microscopy help; C. Ramos, G. Martin, and S. Kupriyanov for assistance in generating mice; and N. Grillet for comments. This work was supported by the NIH (S.J.F., NS060355; U.M., NS046456, MH078833), Generalitat Valenciana (C.G.S., APOSTD/2010/064), Ministerio de Educacion (I.M.G., FU-2006-1238), the Skaggs Institute for Chemical Biology (U.M.), and the Dorris Neurscience Center (U.M.).
PY - 2011/2/10
Y1 - 2011/2/10
N2 - Neuronal migration is critical for establishing neocortical cell layers and migration defects can cause neurological and psychiatric diseases. Recent studies show that radially migrating neocortical neurons use glia-dependent and glia-independent modes of migration, but the signaling pathways that control different migration modes and the transitions between them are poorly defined. Here, we show that Dab1, an essential component of the reelin pathway, is required in radially migrating neurons for glia-independent somal translocation, but not for glia-guided locomotion. During migration, Dab1 acts in translocating neurons to stabilize their leading processes in a Rap1-dependent manner. Rap1, in turn, controls cadherin function to regulate somal translocation. Furthermore, cell-autonomous neuronal deficits in somal translocation are sufficient to cause severe neocortical lamination defects. Thus, we define the cellular mechanism of reelin function during radial migration, elucidate the molecular pathway downstream of Dab1 during somal translocation, and establish the importance of glia-independent motility in neocortical development.
AB - Neuronal migration is critical for establishing neocortical cell layers and migration defects can cause neurological and psychiatric diseases. Recent studies show that radially migrating neocortical neurons use glia-dependent and glia-independent modes of migration, but the signaling pathways that control different migration modes and the transitions between them are poorly defined. Here, we show that Dab1, an essential component of the reelin pathway, is required in radially migrating neurons for glia-independent somal translocation, but not for glia-guided locomotion. During migration, Dab1 acts in translocating neurons to stabilize their leading processes in a Rap1-dependent manner. Rap1, in turn, controls cadherin function to regulate somal translocation. Furthermore, cell-autonomous neuronal deficits in somal translocation are sufficient to cause severe neocortical lamination defects. Thus, we define the cellular mechanism of reelin function during radial migration, elucidate the molecular pathway downstream of Dab1 during somal translocation, and establish the importance of glia-independent motility in neocortical development.
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U2 - 10.1016/j.neuron.2011.01.003
DO - 10.1016/j.neuron.2011.01.003
M3 - Article
C2 - 21315259
AN - SCOPUS:79551670394
SN - 0896-6273
VL - 69
SP - 482
EP - 497
JO - Neuron
JF - Neuron
IS - 3
ER -