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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
Open accessAbstract
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 .
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Cited by
1 Developmental roles and clinical significance of Hedgehog signaling
McMahon, A. P., Ingham, P. W., & Tabin, C. J. (2003) · Current Topics in Developmental Biology · doi:10.1016/s0070-2153(03)53002-2 · Cited by 772
Establishment of vertebrate left–right asymmetry
Hamada, H., Meno, C., Watanabe, D., & Saijoh, Y. (2002) · Nature Reviews Genetics · doi:10.1038/nrg732 · Cited by 489
T HE R OLE OF V ITAMIN A IN M AMMALIAN R EPRODUCTION AND E MBRYONIC D EVELOPMENT
Clagett-Dame, M., & DeLuca, H. F. (2002) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.22.010402.102745e · Cited by 461
Embryonic retinoic acid synthesis is essential for heart morphogenesis in the mouse
Niederreither, K., Vermot, J., Messaddeq, N., Schuhbaur, B., Chambon, P., & Dollé, P. (2001) · Development · doi:10.1242/dev.128.7.1019 · Cited by 420
IFT25 Links the Signal-Dependent Movement of Hedgehog Components to Intraflagellar Transport
Keady, B. T., Samtani, R., Tobita, K., Tsuchya, M., San Agustin, J. T., Follit, J. A., Jonassen, J. A., Subramanian, R., Lo, C. W., & Pazour, G. J. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.04.009 · Cited by 216
Metadata
- Authors
- 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.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1999-09-28
- Volume
- 96
- Issue
- 20
- Pages
- 11376-11381
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2038122444
- Cited by
- 272
- References
- 0
- FWCI
- 6.20
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: 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. https://app.cochat.ai/papers/10.1073/pnas.96.20.11376
- The paper
- 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. https://doi.org/10.1073/pnas.96.20.11376
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