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Fig. 6 (A) siRNA knockdown of CCM2 increases the level of phospho-ERK5 in cultured HUVEC. (B–D) siRNA knockdown of CCM2 increases the expression of KLF2, KLF4, and ADAMTS4 in HUVEC, and these changes in gene expression are reversed by siRNA knockdown of MEKK3 (MAP3K3). Error bars represent SEM. (E and F) Injection of zebrafish embryos with krit1 morpholinos results in a big heart at 72 hpf in i-fabp:GFP transgenic embryos in which the heart is fluorescently labeled. (G) Injection of morpholinos targeting both krit1 and map3k3 rescues the big heart phenotype at 72 hpf. (H) Efficiency of rescue of the krit1 morphant heart phenotype with map3k3 morpholinos. ∗∗∗p < 0.001. (I) Knockdown of map3k3 rescues the cardiac phenotype in ccm2 mutant zebrafish embryos. The frequency of a big heart phenotype in the offspring of ccm2+/− intercrosses treated with control or map3k3 morpholinos is shown. ∗∗∗p < 0.001. The number of total embryos analyzed and number experimental repeats (in parentheses) are indicated above each bar in (H) and (I); Error bars represent SEM. Scale bars represent 100 μm.
Reprinted from Developmental Cell, 32, Zhou, Z., Rawnsley, D.R., Goddard, L.M., Pan, W., Cao, X.J., Jakus, Z., Zheng, H., Yang, J., Arthur, J.S., Whitehead, K.J., Li, D., Zhou, B., Garcia, B.A., Zheng, X., Kahn, M.L., The cerebral cavernous malformation pathway controls cardiac development via regulation of endocardial MEKK3 signaling and KLF expression, 168-80, Copyright (2015) with permission from Elsevier. Full text @ Dev. Cell