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Figure 2


Fig. 2. Ablation of Bmpr1a with Isl1Cre/+ results in embryonic lethality, malformations of heart and limb, and specific reduction of Bmp signaling. (A) Recovery of embryos with the Isl1Cre/+;Bmpr1a f/f genotype. Mendelian frequencies of Isl1Cre/+;Bmpr1a mutants were recovered at E10.5, but began to be lost by E11.5. No mutants were recovered at E14.5. In total 400 embryos were collected and ~50 embryos at each stage. (B-K) Whole-mount morphological analysis of wild-type and mutant littermates. Abnormalities of outflow tract and right ventricle were evident by E8.5 (arrows, B,C,G,H); Hindlimb abnormalities were evident by E10 (N,S; arrows D-F,I-K). (L-U) Bmp signaling as monitored by Bmp-lacZ indicator genetic background. In Isl1Cre/+;Bmpr1a mutants, Bmp signaling was selectively reduced in Isl1-expressing lineages. Bmp signaling was reduced in the outflow tract and right ventricle of Isl1Cre/+;Bmpr1a mutants relative to control littermates (L,M,Q,R). In the hindlimb, Bmp signaling was strongly downregulated in the posterior limb margins (N,O,S,T) and inter hindlimb region (P,U) in Isl1Cre/+;Bmpr1a mutants relative to control littermates. OFT, outflow tract; RV, right ventricle; LV, left ventricle; A, anterior; P, posterior; Lat, lateral view; Dor, dorsal view; Ven, ventral view.





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