Figure 1.

Two mutations in Kmt2d delay early cerebellum development but Kmt2d loss does not drive SHH-MB tumorigenesis

(A) An oncoprint of 127 patient samples considered to be SHH-MB (Kool et al., 2014) using the cBioPortal (Cerami et al., 2012; Gao et al., 2013a) showing the frequency of mutations in KMT2C/D and genes that activate the SHH pathway.

(B) Schematic of mouse Kmt2d^Nf floxed allele with loxP sites surrounding exons 16–19.⁶³

(C) Schematic of mouse Kmt2d^Cf floxed allele with loxP sites surrounding exons 50 and 51.⁶⁴

(D and E) H&E-stained mid-sagittal sections from E18.5 animals of the indicated genotypes with the EGL length in black and convex cerebellar length in red. Scale bars: 500 μm.

(F–I) Quantification at E18.5 of the cerebellar area (mm²) (F and H) and Folding Index ((1-[convex length/EGl length]) x 100) in control (Kmt2d^Nf/+ and Kmt2d^Nf/Nf or Kmt2d^Cf/+ and Kmt2d^Cf/Cf embryos (black dots) or Nes-Cre/+; Kmt2d^Nf/+ or Nes-Cre/+; Kmt2d^Cf/+ (blue dots)) and conditional mutants (red dots) (G and I).

(J–M) Images of H&E-stained mid-sagittal sections from a control and Kmt2d^Cf/Cf conditional mutants using the three Cre drivers at adult stages (P250-P300). Scale bars: 1 mm. Statistical significance was determined using an unpaired t-test. Error bars: SD. Also see Figure S1.