Fig. 1

Cavernomas have clonal origins. Cdh5(PAC)-Cre-ER^T2/R26R-Confetti or Cdh5(PAC)-Cre-ER^T2/Ccm3^fl/fl/R26R-Confetti mice following tamoxifen induction of the four fluorescent proteins and of Ccm3 deletion at 1 day after birth, with analysis at day 8. a Representative images of vessels from retinas of Ccm3^+/+ (upper panel) or Ccm3^−/− (lower panel) mice stained for Isolectin B4. Ccm3^+/+ retina showed random expression of the four fluorophores to form a mosaic; the retina vasculature of Ccm3^−/− mice showed cerebral cavernous malformations and clonal regions composed of cells of the same colour. b Representative images of cerebellum from Ccm3^−/− mice with vessels stained for Podocalyxin (left panel) or Isolectin B4 (central and right panels). Small cavernomas are mostly formed by cells of the same colour, while larger cavernomas show a mixed composition. c Quantification of clonality of the lesions, divided according to small and large lesions on the basis of the longer diameter (cut-off, 60 μm). Lesions were considered clonal when composed of ≥80% cells of the same colour. Each dot represents the percentage of clonal lesions in an animal; data are means ± SE. Source data are provided as a Source Data file. d Representative tiling of the cerebellum from P8 Ccm3^−/− mice with vessels stained for Podocalyxin. e, f Three-dimensional (3D) reconstruction of representative ‘newly formed’, ‘small’, ‘large’ and ‘mulberry’ lesions. CGYR stands for CFP, GFP, YFP and RFP. Scale bars, 100 μm (a, d, f); 50 μm (b); 40 μm (e); white arrows point at lesions. See also Supplementary Movies 1–6 for animated 3D reconstruction of these lesions