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ZFIN ID: ZDB-PUB-000410-1
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
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.
Date: 1999
Source: Proceedings of the National Academy of Sciences of the United States of America   96(20): 11376-11381 (Journal)
Registered Authors: Izpis├║a 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
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.