Extended Data Figure 7: Whole brain MRI reveals many volume changes in the P7 Tox3^−/− mice.

a, P7 Tox3^−/− knockout mouse brains were registered to an average control dataset of P7 Tox3^+/+ (wild-type) brains. The colours correspond to areas of larger (red) and smaller (blue) relative volumes in the knockout embryos. The colour bar minimum corresponds to a false discovery rate (FDR) threshold of 5%. Knockout mice exhibited altered volumes in multiple brain structures including an enlarged pons, amygdala and thalamus/hypothalamus and a decreased pontine nucleus when compared to the wild-type brains (arrows). Most striking was the decrease in the size of the cerebellum of the knockout mice (arrows). (n = 8 Tox3^+/+ versus n = 10 Tox3^−/−, with all 10 showing the defects). Histological analysis of Tox3^−/− mice revealed abnormal development of the cerebellum. b, c, The cerebellum of P7 Tox3^−/− mice is hypoplastic and dysplastic characterized by markedly reduced fissure formation, poor delineation of folia and disorganized cortical structure and layering (c) when compared to the P7 Tox3^+/+ mice (b) (arrows). In some segments, there was complete absence of folial pattern. d, e, Higher magnification revealed that the normally transient external granular layer was absent in the Tox3^−/− mice and the subjacent molecular layer was hypotrophic and irregular in thickness and in multiple foci very thin or absent; in these foci the Purkinje cells extended to the pial surface (arrows). The Purkinje cell layer was also jumbled with no evidence of cell polarity (e).