Fig. 7. Localization and function of TrkB receptors in tangential migration. (A-C) Double immunofluorescence for GFP (A) and TrkB (B) indicates that E14 MGE-GFP cells migrating in the cortical intermediate zone express the TrkB receptor (merged image in C). Note that the TrkB receptor is localized to the leading processes (arrowheads in C) of MGE-GFP cells. (D-F) Effect of inhibiting Trk receptors on migration of GE-GFP cells. (D,E) Confocal images of E14 MGE-GFP cells migrating tangentially into the IZ of early postnatal cortex in the presence of control vehicle (DMSO 1:1000; D) or 50 nM of the Trk tyrosine kinase inhibitor K252a (E). (F) Quantification of the experiments shown in D,E from six slices taken from three independent experiments. Conventions are the same as in Fig. 6E. K252a treatment (red) significantly inhibits migration according to an ANOVA test (F=28.53; P<0.0001). (G-J) Analysis of tangential migration in wild-type and TrkB null mice. (G-H) Low magnification photographs of coronal sections of E15 wild-type (G) and TrkB^–/– mice (H) stained for calbindin 28K. At this rostrocaudal level of section, the global cytoarchitecture of the telencephalon in the two genotypes is indistinguishable. (I-J) High magnification photographs of the lateral cortex of sections shown in G,H. Tangentially migrating calbindin+ cells are found mainly in the subventricular zone (SVZ), the upper part of the intermediate zone (IZ), the subplate (SP) as well as in the marginal zone (MZ) in both wild-type (I) and TrkB^–/– (J) cortex. (K) Quantification of the number of calbindin+ cells per 200 µm wide radial column (indicated by double arrows in G,H). This analysis reveals a significant decrease in the number of tangentially migrating calbindin+ cells in TrkB^–/– cortex compared with TrkB^+/+ cortex at E15 [–32%; **P<0.005 – Mann-Whitney test; 12 sections from three wild-type and three knockout mice]. Scale bars: 15 µm in A-C; 250 µm in D,E, 400 µm in G,H; 120 µm in I,J.