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. 2021 Aug 23;6(16):e146364. doi: 10.1172/jci.insight.146364

Figure 7. Partial depletion of Trp53 exacerbates the presence of cortical heterotopias in Cep135-mutant newborns but not in other MCPH models.

Figure 7

(A) Confocal imaging of a E14.5 Cep135(Δ8/Δ8); Tp53(+/–) neocortex stained with the indicated antibodies. Arrowheads indicate regions of cortical malformations with aberrant folding. Scale bar: 100 μm. (B) Histological Nissl staining of P0 cortices from newborns of the indicated genotypes, showing heterotopias in Cep135(Δ8/Δ8); Trp53(+/–) double mutant newborns (arrowheads). Scale bar: 100 μm. (C) Immunostaining of E14.5 embryonic brain in seriated sagittal sections with the indicated antibodies. Arrowheads in upper confocal images depict regions of cortical malformations (also showed in A). Squared regions depict a cortical heterotopia, showed in higher magnification in lower panels. Scale bars: 100 μm. (D) Higher-magnification confocal images of specific cells from the previous panels showing aberrant and polylobulated nuclei (top arrowheads) and abnormally large nuclei (bottom arrowheads) cells in double mutant heterotopias. A normal nucleus (asterisk) is shown for comparison. Scale bar: 10 μm. (E) Immunostaining of P0 neocortices of the indicated genotypes against SATB2 (layers II–V), CTIP2 (layer V), and TBR1 (layer VI). Note the presence of CTIP2+, TBR1+, SATB2– subcortical heterotopias. Scale bar: 100 μm (left panels) and 50 μm (higher-magnification panels to the right).