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

Tohru Tsukui, Javier Capdevila, Koji Tamura, Pilar Ruiz-Lozano, Concepción Rodriguez-Esteban, Sayuri Yonei-Tamura, Jorge Magallón, Roshantha A.S. Chandraratna, Kenneth Chien, Bruce Blumberg, Ronald M. Evans, Juan Carlos Izpisúa Belmonte

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221 Citations (Scopus)

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 laterally 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.

Original languageEnglish
Pages (from-to)11376-11381
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number20
DOIs
Publication statusPublished - 1999 Sep 28

ASJC Scopus subject areas

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    Tsukui, T., Capdevila, J., Tamura, K., Ruiz-Lozano, P., Rodriguez-Esteban, C., Yonei-Tamura, S., Magallón, J., Chandraratna, R. A. S., Chien, K., Blumberg, B., Evans, R. M., & Belmonte, J. C. I. (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. https://doi.org/10.1073/pnas.96.20.11376