Fig. 1: Defective migration of MGE-derived cortical INs in Trio–/– embryos. | Molecular Psychiatry

Fig. 1: Defective migration of MGE-derived cortical INs in Trio–/– embryos.

From: Both GEF domains of the autism and developmental epileptic encephalopathy-associated Trio protein are required for proper tangential migration of GABAergic interneurons

Fig. 1

Lhx6 in situ hybridization on e14.5 coronal brain sections in control (A) and Trio–/– (B) embryos. C Histogram showing the distribution of Lhx6+ signal in the dorsal pallium of e14.5 control and Trio–/– embryos. Bins are delineated by the dotted lines in (A, B). D Histogram showing the radial distribution of Lhx6+ signal in the dorsal pallium of e14.5 control and Trio–/– embryos. Neocortical layers (MZ, IZ and SVZ) are delineated by the small boxes in (A, B) (n = 5 control and 3 Trio–/– embryonic brains). Lhx6 in situ hybridization on e18.5 coronal brain sections in control (E) and Trio-/- (F) embryos. G Lhx6+ signal distribution within the e18.5 somatosensory neocortical layers in control and Trio–/– embryos (n = 3 control and 3 Trio-/- embryonic brains). H–J Proliferation in the MGE is not affected at e12.5 in Trio–/– embryos. Representative images showing EdU incorporation (red) in MGE proliferative cells 2 h after EdU injection at e12.5, together with Hoechst staining (blue), in control (H) and Trio–/– embryos (I). J Histogram showing the percentage of the VZ, SVZ and MaZ area covered by EdU+ signal (n = 4 control and 4 Trio–/– embryonic brains). K–O Reduced migration of Trio–/– MGE-derived INs in MGE explant cultures. Representative immunofluorescence images of control (K, L) and Trio–/– (M, N) MGE explants generated at e14.5 and cultured for 48 h. O Histogram showing the mean maximal distance traveled by control and Trio–/– MGE-derived INs in cultured explants (n = 11 explants from 2 control brains and 12 explants from 2 Trio–/– brains, statistical comparisons conducted on the number of explants per genotypes). P–U Impaired growth cone morphology in Trio–/– MGE-derived INs. Representative illustrations for growth cone complex morphology (P, R) and collapsed morphology (Q, S) in control (P, Q) and Trio–/– (R, S) INs from MGE explants. T Histogram showing the number of control and Trio–/– MGE-derived INs with a complex or a collapsed morphology (n = 766 growth cones from 3 control brains and 565 growth cones from 3 Trio–/– brains). U Histogram showing the mean growth cone surface of control and Trio–/– MGE-derived INs with a complex morphology (n = 173 growth cones from 3 control brains and 65 growth cones from 3 Trio–/– brains). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 by two-way ANOVA followed by Bonferroni’s multiple comparison’s test (C, D, G, J), by Mann–Whitney test (O, U) or by Fisher’s exact test (T). Data are represented as mean ± SEM, except for (T). CP cortical plate, Ctrl control, IZ intermediate zone, MaZ mantle zone, MZ marginal zone, SVZ subventricular zone, UL upper layer, VZ ventricular zone. Scale bars: 500 μm (B), 250 μm (F, I) 150 μm (N) and 10 μm (S).

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