, 2010). One possibility is that Reelin might change the subcellular localization of N-cadherin during terminal translocation

to cooperatively regulate terminal translocation with integrin α5β1, because previous immunohistochemical analyses have revealed intense N-cadherin staining in the MZ (Franco et al., 2011), but only weak staining on the top of the CP (Kawauchi et al., 2010). Alternatively, there is the other possibility that VE-822 cell line the mechanisms underlying terminal translocation are different from those of somal translocation, because neurons need to pass through the cell-dense PCZ during terminal translocation, unlike the cell-sparse preplate in the case of neurons showing somal translocation (Sekine et al., 2011). How does activated integrin α5β1 regulate terminal translocation? Because the cell somata are thought to be pulled with shortening of the leading processes and because activated integrin β1 is strongly localized in the leading processes, which anchor to the fibronectin-positive

MZ, we hypothesize that traction forces are generated at the leading processes through the integrin α5β1 “outside-in” signaling. A recent in vitro study supported this model by showing the presence of traction forces at the tips of the leading processes (He et al., 2010). Our data also showed that Akt plays some role in terminal translocation, which is consistent with a previous finding that Reelin reorganizes the actin cytoskeletons in the leading processes this website through phosphorylation of n-cofilin via Akt (Chai et al., 2009). Microtubules in the leading processes must also be reorganized for the shortening of the leading process, and the microtubule dynamics is also coupled to the

forward movement of the nuclei (Tsai and Gleeson, 2005; Zhang et al., 2009). Therefore, we reason that the leading processes play the primary role in the terminal translocation of the neocortical neurons. crotamiton However, recent in vitro analyses of neuronal migration under the Matrigel condition, in which radial glial fibers do not exist, suggested that there is also the other possibility that the contraction of myosin II behind the nuclei and endocytosis of adhesion molecules just proximal to the cell somata are involved in the pushing up of the cell somata (Schaar and McConnell, 2005; Shieh et al., 2011). Future in vivo studies will be needed to elucidate the detailed mechanisms underlying neuronal migration in the neocortex, which will lead to revelation of the complex mechanisms of neuronal layer formation. Pregnant ICR mice were purchased from Japan SLC (Shizuoka, Japan). The colony of reeler mice (B6CFe a/a-Relnrl/J) obtained from the Jackson Laboratory (Bar Harbor, ME) was maintained by allowing heterozygous females to mate with homozygous males. The day of vaginal plug detection was considered to be embryonic day 0 (E0).