The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure
Abstract
The murine dishevelled 2 (Dvl2) gene is an ortholog of theDrosophila segment polarity gene Dishevelled, a member of the highly conserved Wingless/Wnt developmental pathway.Dvl2-deficient mice were produced to determine the role ofDvl2 in mammalian development. Mice containing null mutations inDvl2 present with 50% lethality in both inbred 129S6 and in a hybrid 129S6-NIH Black Swiss background because of severe cardiovascular outflow tract defects, including double outlet right ventricle, transposition of the great arteries and persistent truncus arteriosis. The majority of the surviving Dvl2-/- mice were female, suggesting that penetrance was influenced by sex. Expression of Pitx2 and plexin A2 was attenuated in Dvl2 null mutants, suggesting a defect in cardiac neural crest development during outflow tract formation. In addition, ∼90%of Dvl2-/- mice have vertebral and rib malformations that affect the proximal as well as the distal parts of the ribs. These skeletal abnormalities were more pronounced in mice deficient for both Dvl1and Dvl2. Somite differentiation markers used to analyzeDvl2-/- and Dvl1-/-;Dvl2-/-mutant embryos revealed mildly aberrant expression of Uncx4.1, delta 1 and myogenin, suggesting defects in somite segmentation. Finally, 2-3% ofDvl2-/- embryos displayed thoracic spina bifida, while virtually all Dvl1/2 double mutant embryos displayed craniorachishisis, a completely open neural tube from the midbrain to the tail. Thus, Dvl2 is essential for normal cardiac morphogenesis,somite segmentation and neural tube closure, and there is functional redundancy between Dvl1 and Dvl2 in some phenotypes.
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Metadata
- Authors
- Hamblet, N. S., Lijam, N., Ruiz-Lozano, P., Wang, J., Yang, Y., Luo, Z., Mei, L., Chien, K. R., Sussman, D. J., & Wynshaw-Boris, A.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2002-12-15
- Volume
- 129
- Issue
- 24
- Pages
- 5827-5838
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2045751117
- Cited by
- 441
- References
- 70
- FWCI
- 6.16
- Type
- journal article
- Language
- en
- Open access
- closed
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