HEART AND EXTRAEMBRYONIC MESODERMAL DEFECTS IN MOUSE EMBRYOS LACKING THE BHLH TRANSCRIPTION FACTOR HAND1

The basic helix-loop-helix (bHLH) transcription factors, Hand1 and Han d2 (refs 1,2), also called eHand/Hxt/Thing1 and dHand/Hed/Thing2 (refs 3,4), respectively, are expressed in the heart and certain neural-cre st derivatives during embryogenesis. In addition, Hand1 is expressed i n extraembryonic membranes, whereas Hand2 is expressed in the deciduum . Previous studies have demonstrated that Hand2 is required for format ion of the right ventricle of the heart and the aortic arch arteries(5 ). We have generated a germline mutation in the mouse Hand1 gene by re placing the first coding exon with a beta-galactosidase reporter gene. Embryos homozygous for the Hand1 null allele died between embryonic d ays 8.5 and 9.5 and exhibited yolk sac abnormalities due to a deficien cy in extraembryonic mesoderm, Heart development was also perturbed an d did not progress beyond the cardiac-looping stage. Our results demon strate important roles for Hand1 in extraembryonic mesodermal and hear t development.