PLEIOTROPIC EFFECTS OF THE CARDIAC-LETHAL GENE IN THE AXOLOTL (AMBYSTOMA-MEXICANUM)

Embryos of the axolotl affected with the cardiac-lethal mutation form hearts that never begin to beat. A number of other traits characterist ic of the mutant phenotype, including edema, underdeveloped gills, sho rter stature, and aphagia (the inability to feed), were believed to be secondary effects of the absence of circulation. We have recently dem onstrated that the pre-cardiac mesoderm is directly affected by the c gene, making it unresponsive to normal inductive signals. In this stud y, we replaced part or all of the mutant pre-cardiac mesoderm with wil d-type tissue, to produce embryos with normally beating hearts and cir culation. As expected, most of the other mutant characteristics were a lso corrected. However, otherwise normal individuals remained aphagic. All embryos with beating hearts containing mutant tissue also suffere d from an unexpected circulatory arrest some time after the onset of c irculation. This apparently indicates that there are at least two tiss ues other than the myocardium which appear to be directly affected by the c gene. These previously unsuspected pleiotropic effects of the mu tation may involve poorly-characterized mesodermal-neural crest induct ive interactions and may also lead to a greater understanding of the l ink between congenital heart defects and feeding difficulties in human s. (C) 1993 Wiley-Liss, Inc.