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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.