PUBLICATION
Multiple left-right asymmetry defects in Shh(-/-) mutant mice unveil a convergence of the shh and retinoic acid pathways in the control of Lefty-1
- Authors
- Tsukui, T., Capdevila, J., Tamura, K., Ruiz-Lozano, P., Rodriguez-Esteban, C., Yonei-Tamura, S., Magallon, J., Chandraratna, R.A., Chien, K., Blumberg, B., Evans, R.M., and Belmonte, J.C.
- ID
- ZDB-PUB-000410-1
- Date
- 1999
- Source
- Proceedings of the National Academy of Sciences of the United States of America 96(20): 11376-11381 (Journal)
- Registered Authors
- Izpisúa Belmonte, Juan Carlos
- Keywords
- none
- MeSH Terms
-
- Animals
- Base Sequence
- Chick Embryo
- Congenital Abnormalities/etiology*
- Gene Expression Regulation, Developmental*
- Hedgehog Proteins
- Left-Right Determination Factors
- Mice
- Mice, Knockout
- Molecular Sequence Data
- Proteins/physiology*
- RNA, Messenger/analysis
- Trans-Activators*
- Transforming Growth Factor beta/genetics*
- Tretinoin/physiology*
- PubMed
- 10500184 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Tsukui, T., Capdevila, J., Tamura, K., Ruiz-Lozano, P., Rodriguez-Esteban, C., Yonei-Tamura, S., Magallon, J., Chandraratna, R.A., Chien, K., Blumberg, B., Evans, R.M., and Belmonte, J.C. (1999) Multiple left-right asymmetry defects in Shh(-/-) mutant mice unveil a convergence of the shh and retinoic acid pathways in the control of Lefty-1. Proceedings of the National Academy of Sciences of the United States of America. 96(20):11376-11381.
Abstract
Asymmetric expression of Sonic hedgehog (Shh) in Hensen's node of the chicken embryo plays a key role in the genetic cascade that controls left-right asymmetry, but its involvement in left-right specification in other vertebrates remains unclear. We show that mouse embryos lacking Shh display a variety of laterality defects, including pulmonary left isomerism, alterations of heart looping, and randomization of axial turning. Expression of the left-specific gene Lefty-1 is absent in Shh(-/-) embryos, suggesting that the observed laterality defects could be the result of the lack of Lefty-1. We also demonstrate that retinoic acid (RA) controls Lefty-1 expression in a pathway downstream or parallel to Shh. Further, we provide evidence that RA controls left-right development across vertebrate species. Thus, the roles of Shh and RA in left-right specification indeed are conserved among vertebrates, and the Shh and RA pathways converge in the control of Lefty-1.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping