Here, we confirmed using in situ hybridization that Shh is already expressed in the PI3K Inhibitor Library research buy IZ of the cortical
wall at E14.5 ( Figure 8E1), the stage when MGE cells start to colonize the cortical plate. The expression pattern of Shh is compatible with local and discrete modulation of leading processes properties all along the migratory pathway of MGE cells ( Figure 8E2). Our study shows that the mother centriole of tangentially migrating GABA neurons assembles a primary cilium and docks to the plasma membrane through this primary cilium. The primary cilium of tangentially migrating GABA neurons is functional and transduces local Shh signal that promotes GABA neurons reorientation from tangential migratory streams toward the cortical plate (CP). Using complementary genetic models, we show that functional anterograde
IFT is required for Shh dependent reorientation of interneurons toward the CP during embryonic development and influences cortex colonization by GABA neurons. It is established that the CTR controls the neuronal migration through its MTOC function (Higginbotham and Gleeson, see more 2007). In tangentially migrating MGE cells, the CTR anchors a MT network distinct from extracentrosomal MTs. The centrosomal array of MTs is reminiscent of the cage of perinuclear MTs described in radially migrating neurons (Rivas and Hatten, 1995; Solecki et al., 2004; Tsai et al., 2007). Bundles of extracentrosomal MTs extend in front of the nucleus, as already described in cerebellar neurons (Umeshima et al., 2007). This MT organization into two networks should support quick changes in the relative positioning of the CTR and nucleus and should permit independent movements of the CTR toward the plasma membrane, allowing fusion between the centriolar vesicle and the plasma membrane.
Plasma membrane docking of the mother centriole should position the centrosomal network of MTs on one side of the leading process, thereby influencing almost cell directionality. Strong correlation between the subcellular location of the mother centriole and its distance to the nucleus suggests that the mother centriole is not permanently docked to the plasma membrane during the migratory cycle. Rather, the primary cilium is successively addressed and removed from the cell surface by fusion/fission of the centriolar vesicle. An important question for the future will be to understand how the subcellular localization of the mother centriole during the migration cycle is correlated to ciliogenesis and to trajectory decisions. The primary cilium of MGE cells varied in length depending on the substratum of migration. Differences could result from difference in adhesive interactions between MGE cells and their migratory substratum since it has been shown that contact interactions and the distribution of tension forces affect primary cilium length in adhesive mammalian cells (Pitaval et al., 2010).