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Pharmacological Notch inhibition decreases the penetrance of <italic>mef2ca</italic>-associated phenotypes without producing a skeletal phenotype in genetic wild types.(A) Animals heterozygous for mef2ca from the high-penetrance strain were intercrossed and offspring treated with Notch inhibitor (DBZ) or vehicle control (DMSO) from 18–48 hpf. Treated animals were fixed and stained with Alcian Blue (cartilage) and Alizarin Red (bone) at 6 dpf. Genotyped skeletal preparations were scored for penetrance of mef2ca-associated phenotypes. Asterisks indicate significance at alpha = 0.05 Fisher’s exact test compared with DMSO. (B) Imaged flat mounts of dissected skeletons from stained, genotyped animals treated with DMSO or DBZ were imaged. Arrows indicate dysmorphic ch and arrowheads mark ectopic bone. Scale bar: 50 μm. (C) Animals heterozygous for mef2ca from an unselected strain were intercrossed and offspring treated with either DMSO from 18–48 hpf, or Notch inhibitor (DBZ) from 18–30, or DBZ from 30–48 hpf. Treated animals were fixed and stained with Alcian Blue (cartilage) and Alizarin Red (bone) at 6 dpf. Genotyped skeletal preparations were scored for penetrance of mef2ca-associated phenotypes. Asterisks indicate significance at alpha = 0.05 Fisher’s exact test compared with DMSO.
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