WILD-TYPE ENDODERM ABROGATES THE VENTRAL DEVELOPMENTAL DEFECTS ASSOCIATED WITH GATA-4 DEFICIENCY IN THE MOUSE

GATA-4 knockout mice die by 9.5 days postcoitum and exhibit profound d efects in ventral morphogenesis, including abnormal foregut formation and a failure of fusion of the bilateral myocardial primordia. During early mouse development, GATA-4 is expressed in cardiogenic splanchnic mesoderm and associated endoderm, suggesting that the presence of thi s transcription factor in one or both of these tissue types is essenti al for ventral development. To distinguish whether GATA-4 expression i n mesoderm or endoderm accounts for the phenotype of the knockout mous e, we prepared chimeric mice by injecting Gata4-/- ES cells into 8-cel l stage ROSA26(Gata4+/+) embryos. We identified a series of high perce ntage null chimeras (8-10 days postcoitum) in which Gata4+/+ cells wer e restricted to visceral yolk sac endoderm and small portions of the f oregut/hindgut endoderm. Despite an absence of GATA-4 in all other cel ls of these embryos, there was normal development of the heart, foregu t, and surrounding tissues. We conclude that expression of GATA-4 in e ndoderm rather than cardiogenic mesoderm is required for ventral morph ogenesis. (C) 1997 Academic Press.