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.