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. 2015 Dec 3;4:e12703. doi: 10.7554/eLife.12703

Figure 4. H1047R mutant mice display abnormal neocortical layering.

(a) Schematics of mouse brain and section; section corresponds to the marked coronal plane; red box in the section marks the area of neocortex (nctx) depicted in the images below. (b–g) and (h–m) correspond to ages E16.5 and P3 respectively. In control cortex, Reelin is in layer I (b), Ctip2 and Tbr1 in deep layers VI and V (d,j), Cux1 in upper layers II-IV (f,l) and NeuN in all matured neurons (h). H1047R mutants displayed abnormal distribution of cells for all neocortical layers, observed at E16.5 and P3 (c,e,g,i,k,m). (b’,c’) Magnified view of Reelin-positive cells in control and H1047R mutant. P3 H1047R mutant showed enlarged area between ventricular zone (vz) and cortical plate and absence of clear subplate (sp) boundary (h-k). A, anterior; P, posterior; yellow dashed lines, lateral ventricular lining; white dotted lines, pial surface; I-VI, neocortical layers; arrowheads, mispositioned mutant cells. Scale bars: 25 μm (b’,c’), 50 μm (b-i), 150 μm (j-o). See also Figure 4—figure supplements 1–2.

DOI: http://dx.doi.org/10.7554/eLife.12703.011

Figure 4.

Figure 4—figure supplement 1. Nestin expression in hGFAP-cre; H1047R mutant.

Figure 4—figure supplement 1.

Nestin-positive radial glial fibres appeared slightly irregular and hyperfasciculated in E14.5 H1047R mutant (b) but show progressively dysplastic morphology at E16.5 (d) and P0 (f), compared to respective controls (a,c,e). Yellow boxes (e,f) show broken pia and disrupted radial glial end-feet in the P0 H1047R mutant (f). Arrows indicate Nestin-fibers crossed the broken pial surface in the mutant. Scale bars: 50 μm (a,b), 150 μm (c-f).
DOI: http://dx.doi.org/10.7554/eLife.12703.012
Figure 4—figure supplement 2. hGFAP-cre;H1047R mutant displays distinct white matter dysplasia.

Figure 4—figure supplement 2.

Nissl-stained coronal sections of P3 control (a,c,e) and mutant (b,d,f) brains; areas with faint or absence of Nissl stain consist of axon fibre tracts. (a,b) and (c,d) show two comparable antero-posterior planes of section between control and H1047R (hGFAP-cre;H1047R) mutant. (a,c) P3 Control sections showed presence of anterior commissure (black arrow), corpus callosum (cc) and hippocampal commissure (hc). H1047R mutants lacked corpus callosum (asterisk, b) while other commissures were present (d). Magnified view of neocortex showed expansion of white matter (wm) areas in H1047R mutant compared to control (e,f). (ei) and (fi) correspond to the dotted boxes in e and f respectively, illustrating presence of increased number of Olig2-positive cells in the expanded white matter area of H1047R mutant. The mutant also had an unclear subplate boundary (white dotted line; f, fi), which is normally seen in the control (sp; e, ei). CP, cortical plate; vz, ventricular zone. Scale bars: 50 μm (ei,fi); 300 μm (e,f); 1 mm (a-d).
DOI: http://dx.doi.org/10.7554/eLife.12703.013