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We report that Id knockout mouse embryos display multiple cardiac defects, but mid-gestation lethality is rescued by the injection of 15 wild-type embryonic stem (ES) cells into mutant blastocysts. Myocardial markers altered in Id mutant cells are restored to normal throughout the chimeric myocardium. Intraperitoneal injection of ES cells into female mice before conception also partially rescues the cardiac phenotype with no incorporation of ES cells. Insulin-like growth factor 1, a long-range secreted factor, in combination with WNT5a, a locally secreted factor, likely account for complete reversion of the cardiac phenotype. Thus, ES cells have the potential to reverse congenital defects through Id-dependent local and long-range effects in a mammalian embryo., The Id proteins are dominant negative antagonists of basic helix-loop-helix (bHLH) transcription factors and regulate differentiation in multiple lineages (1). Previous studies have shown that Id1 to Id4 are expressed [...]

The bilateral cardiac mesoderm migrates from the lateral region of the embryo to the ventral midline, where it fuses to form the primitive heart tube. It is generally accepted that migration and fusion are essential for subsequent stages of cardiac morphogenesis. We present evidence that, in Foxp4 mutant embryonic mice, each bilateral heart-forming region is capable of developing into a highly differentiated four-chambered mammalian heart in the absence of midline fusion. These data demonstrate that left-right chamber specification, cardiac looping, septation, cardiac myocyte differentiation, and endocardial cushion formation are preprogrammed in the precardiac mesoderm and do not require midline positional identity or heart tube fusion., Although the molecular mechanisms underlying cardiac myocyte differentiation have been extensively examined and initial molecular pathways have been identified, much less is understood about how specified myocardial cells form the [...]