Odd-skipped related 1 (Odd 1) is an essential regulator of heart and urogenital development.
The Odd-skipped related 1 (Odd 1) gene encodes a zinc finger protein homologous to the Drosophila Odd-skipped class transcription factors that play critical roles in embryonic patterning and tissue morphogenesis. We have generated mice carrying a targeted null mutation in the Odd 1 gene and show that Odd 1 is essential for heart and intermediate mesoderm development. Odd 1(-/-) mutant mouse embryos fail to form atrial septum, display dilated atria with hypoplastic venous valves, and exhibit blood backflow from the heart into systemic veins. In contrast to other transcription factors implicated in atrial septum development, Odd 1 mRNA expression is restricted to the central dorsal domain of the atrial myocardium during normal heart development. Moreover, expression patterns of known key regulatory genes of atrial septum development, including Nkx2.5, Pitx2, and Tbx5, are unaltered in the developing heart in Odd 1(-/-) mutants compared to that of the wild-type littermates. Furthermore, homozygous Odd 1(-/-) mutant embryos exhibit complete agenesis of adrenal glands, metanephric kidneys, gonads, and defects in pericardium formation. Detailed molecular marker analyses show that key regulators of early intermediate mesoderm development, including Lhx1, Pax2, and Wt1, are all down-regulated and nephrogenic mesenchyme undergoes massive apoptosis, resulting in disruption of nephric duct elongation and failure of metanephric induction in the Odd 1(-/-) mutant embryos. These data provide new insights into the molecular mechanisms underlying heart morphogenesis and urogenital development.
Wang
Qingru
Q
Center for Oral Biology and Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 611, Rochester, NY 14642, USA.
Lan
Yu
Y
Cho
Eui-Sic
ES
Maltby
Kathleen M
KM
Jiang
Rulang
R
D000311:Adrenal Glands / Q000196:embryology / Q000378:metabolism; D000818:Animals; D047108:Embryonic Development; D006321:Heart / Q000196:embryology*; D006346:Heart Septum / Q000196:embryology / Q000378:metabolism; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D060850:LIM-Homeodomain Proteins; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D051762:PAX2 Transcription Factor / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014566:Urogenital System / Q000196:embryology / Q000378:metabolism*; D025721:WT1 Proteins / Q000378:metabolism; D000097577:Homeobox Protein PITX2
D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009687:Nuclear Proteins; D051762:PAX2 Transcription Factor; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D025721:WT1 Proteins; D000097577:Homeobox Protein PITX2; C499523:Lhx1 protein, mouse; C484469:Nkx2-5 protein, mouse; C121641:Osr1 protein, mouse; C497319:Pax2 protein, mouse; C103172:T-box transcription factor 5