Heart and extra-embryonic mesodermal defects in mouse embryos lacking the bHLH transcription factor Hand1.
The basic helix-loop-helix (bHLH) transcription factors, Hand1 and Hand2 (refs 1,2), also called eHand/Hxt/Thing1 and dHand/Hed/Thing2 (refs 3,4), respectively, are expressed in the heart and certain neural-crest derivatives during embryogenesis. In addition, Hand1 is expressed in extraembryonic membranes, whereas Hand2 is expressed in the deciduum. Previous studies have demonstrated that Hand2 is required for formation of the right ventricle of the heart and the aortic arch arteries. We have generated a germline mutation in the mouse Hand1 gene by replacing the first coding exon with a beta-galactosidase reporter gene. Embryos homozygous for the Hand1 null allele died between embryonic days 8.5 and 9.5 and exhibited yolk sac abnormalities due to a deficiency in extraembryonic mesoderm. Heart development was also perturbed and did not progress beyond the cardiac-looping stage. Our results demonstrate important roles for Hand1 in extraembryonic mesodermal and heart development.
Firulli
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AB
Department of Molecular Biology, The University of Texas Southwestern Medical Center at Dallas, 75235-9148, USA.
McFadden
D G
DG
Lin
Q
Q
Srivastava
D
D
Olson
E N
EN
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology*; D005313:Fetal Death / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D018398:Homeodomain Proteins; D006720:Homozygote; D017403:In Situ Hybridization; D008648:Mesoderm / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009206:Myocardium / Q000473:pathology; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D051857:Otx Transcription Factors; D010928:Placental Lactogen / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014327:Trophoblasts
D009320:Atrial Natriuretic Factor; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D018994:Myosin Light Chains; D009419:Nerve Tissue Proteins; D051857:Otx Transcription Factors; D010928:Placental Lactogen; D015534:Trans-Activators; D014157:Transcription Factors; C095572:Hand1 protein, mouse; C097341:helix-loop-helix protein, eHAND; C085699:placental lactogen I, rat