期刊
DEVELOPMENTAL BIOLOGY
卷 288, 期 2, 页码 582-594出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2005.09.024
关键词
adrenal gland; atrial septum; heart development; intermediate mesoderm; kidney development; odd-skipped; Osr1; renal agenesis; venous valve
资金
- NIDCR NIH HHS [R01 DE013681-05, R01 DE013681, R01DE013681, R01 DE013681-04, R01 DE013681-06] Funding Source: Medline
The Odd-skippedrelated1 (Odd1)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 Odd1 gene and show that Odd1 is essential for heart and intermediate mesoderm development. Oddl(-/-) mutant mouseembryos 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, Odd1 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 Nkv2,5, llitv2 and Thv5, are unaltered in the developing heart in Odd1 - mutants compared to that of the wild-type littermates. Furthermore, homozygous Odd1 mutant embryos exhibit complete agenesis of adrenal glands, metanephric kidneys, gonads, and defects impericardium formation. Detailed molecularn marker analyses show that key regulators of early intermediate mesoderm development, including Lhxl, Pax2, and Wt 1, are all down-regulated and nephrogenie mesenchyme undergoes massive apoptosis, resulting in disruption of nephric duct elongation and failure of rnetanephric induction in the Odd1 mutant embryos. These data provide new insights into the molecular mechanisms underlying heart morphogenesis and Urogenital development. (c) 2005 Elsevier Inc. All rights reserved.
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