Fig. 9.

Irf6 and Esrp1/2 interact to modify palate phenotypes. Mice compound heterozygous for Irf6^R84C, Esrp1 and Esrp2 were generated by breeding Irf6^R84C/+ with Esrp1^+/−; Esrp2^−/− mice. The triple heterozygotes were then inter-crossed and embryos were collected at E18.5. (A) Representative lateral, frontal and oral images of embryos, comparing WT (Irf6^+/+; Esrp1^+/+; Esrp2^+/+), Irf6^R84C heterozygote (Het) (Irf6^R84C/+; Esrp1^+/+; Esrp2^+/+), Esrp1/2 double heterozygote (Irf6^+/+; Esrp1^+/−; Esrp2^+/−) and triple heterozygote (Irf6^R84C/+; Esrp1^+/−; Esrp2^+/−). (B) Measurements of palate length (L) relative to width (W). Irf6^R84C/+ embryos tend to have a shorter palate compared with WT; however this genotype on an Esrp1^+/−; Esrp2^+/− background results in significantly increased palate length relative to Irf6^R84C/+; Esrp1^+/+; Esrp2^+/+ (one-way ANOVA, *P<0.05; n=3,5,6,9). (C) Representative frontal and oral images of embryos, comparing Irf6^+/+; Esrp1^−/−; Esrp2^+/− with Irf6^R84C/+; Esrp1^−/−; Esrp2^+/− and Irf6^+/+; Esrp1^−/−; Esrp2^−/− with Irf6^R84C/+; Esrp1^−/−; Esrp2^−/−. Scale bars: 50 μm. (D) Hematoxylin and Eosin staining of coronal sections through the vomeronasal cavity and primary palate of the same embryos. Irf6^R84C heterozygosity modifies the Esrp1 knockout (KO) and Esrp1/2 double KO cleft lip and palate such that the cleft space between adjacent elements is narrower (arrowheads; C,D), and, in some cases, we noticed epithelial adhesions that limited the cleft. Scale bars: 100 μm.