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 .
Bibliography
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 â/â 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, 96(20), 11376â11381.
Authors
12
- Tohru Tsukui (first)
- Javier Capdevila (additional)
- Koji Tamura (additional)
- Pilar Ruiz-Lozano (additional)
- Concepción Rodriguez-Esteban (additional)
- Sayuri Yonei-Tamura (additional)
- Jorge Magallón (additional)
- Roshantha A. S. Chandraratna (additional)
- Kenneth Chien (additional)
- Bruce Blumberg (additional)
- Ronald M. Evans (additional)
- Juan Carlos Izpisúa Belmonte (additional)
References
31
Referenced
233
-
R P Harvey Cell 94, 273–276 (1998).
(
10.1016/S0092-8674(00)81468-3
) / Cell by Harvey R P (1998) -
M Levin, R L Johnson, C D Stern, M Kuehn, C Tabin Cell 82, 803–814 (1995).
(
10.1016/0092-8674(95)90477-8
) / Cell by Levin M (1995) -
A K Ryan, B Blumberg, C Rodriguez-Esteban, S Yonei-Tamura, K Tamura, T Tsukui, J de la Peña, W Sabbagh, J Greenwald, S Choe, et al. Nature (London) 394, 545–551 (1998).
(
10.1038/29004
) / Nature (London) by Ryan A K (1998) -
C Meno, A Shimono, Y Saijoh, K Yashiro, K Mochida, S Ohishi, S Noji, H Kondoh, H Hamada Cell 94, 287–297 (1998).
(
10.1016/S0092-8674(00)81472-5
) / Cell by Meno C (1998) -
S M Pagán-Westphal, C J Tabin Cell 93, 25–35 (1998).
(
10.1016/S0092-8674(00)81143-5
) / Cell by Pagán-Westphal S M (1998) -
C Chiang, Y Litingtung, E Lee, K E Young, J L Corden, H Westphal, P A Beachy Nature (London) 383, 407–413 (1996).
(
10.1038/383407a0
) / Nature (London) by Chiang C (1996) -
M H Zile J Nutr 128, 455S–488S (1998).
(
10.1093/jn/128.2.455S
) / J Nutr by Zile M H (1998) -
X Wang, P Penzes, J L Napoli J Biol Chem 271, 16288–16293 (1996).
(
10.1074/jbc.271.27.16288
) / J Biol Chem by Wang X (1996) -
D Zhao, P McCaffery, K J Ivins, R L Neve, P Hogan, W W Chin, U C Drager Eur J Biochem 240, 15–22 (1996).
(
10.1111/j.1432-1033.1996.0015h.x
) / Eur J Biochem by Zhao D (1996) -
K Niederreither, P McCaffery, U C Drager, P Chambon, P Dolle Mech Dev 62, 67–78 (1997).
(
10.1016/S0925-4773(96)00653-3
) / Mech Dev by Niederreither K (1997) -
K Niederreither, V Subbarayan, P Dolle, P Chambon Nat Genet 21, 444–448 (1999).
(
10.1038/7788
) / Nat Genet by Niederreither K (1999) - M Fujinaga Int J Dev Biol 41, 153–186 (1997). / Int J Dev Biol by Fujinaga M (1997)
- J N Thompson The Fat Soluble Vitamins, eds H F De Luca, J W Suttie (Univ. of Wisconsin Press, Madison), pp. 267–281 (1969). / The Fat Soluble Vitamins by Thompson J N (1969)
-
H Dersch, M H Zile Dev Biol 160, 424–433 (1993).
(
10.1006/dbio.1993.1318
) / Dev Biol by Dersch H (1993) - D A T New Postimplantation Mammalian Embryos: A Practical Approach, eds A J Copp, D L Cockcroft (IRL, Oxford), pp. 1–15 (1990). / Postimplantation Mammalian Embryos: A Practical Approach by New D A T (1990)
-
A T Johnson, E S Klein, S J Gillett, L Wang, T K Song, M E Pino, R A Chandraratna J Med Chem 38, 4764–4767 (1995).
(
10.1021/jm00024a003
) / J Med Chem by Johnson A T (1995) - , ed D G Wilkinson (Oxford Univ. Press, Oxford In Situ Hybridization, 1993). / In Situ Hybridization by Wilkinson D G (1993)
-
J R Marszalek, P Ruiz-Lozano, E Roberts, K R Chien, L S Goldstein Proc Natl Acad Sci USA 96, 5043–5048 (1999).
(
10.1073/pnas.96.9.5043
) / Proc Natl Acad Sci USA by Marszalek J R (1999) - D A T New J Embryol Exp Morphol 3, 326–331 (1955). / J Embryol Exp Morphol by New D A T (1955)
-
C D Stern, R T Yu, A Kakizuka, C R Kintner, L S Mathews, W W Vale, R M Evans, K Umesono Dev Biol 172, 192–205 (1995).
(
10.1006/dbio.1995.0015
) / Dev Biol by Stern C D (1995) -
R S Ross, S Navankasattusas, R P Harvey, K R Chien Development (Cambridge, UK) 122, 1799–1809 (1996).
(
10.1242/dev.122.6.1799
) / Development (Cambridge, UK) by Ross R S (1996) -
Y Litingtung, L Lei, H Westphal, C Chiang Nat Genet 20, 58–61 (1998).
(
10.1038/1717
) / Nat Genet by Litingtung Y (1998) -
S M Smith, E D Dickman, R P Thompson, A R Sinning, A M Wunsch, R R Markwald Dev Biol 182, 162–171 (1997).
(
10.1006/dbio.1996.8474
) / Dev Biol by Smith S M (1997) -
W Twal, L Roze, M H Zile Dev Biol 168, 225–234 (1995).
(
10.1006/dbio.1995.1075
) / Dev Biol by Twal W (1995) -
Y Chen, D Dong, I Kostetskii, M H Zile Dev Biol 173, 256–264 (1996).
(
10.1006/dbio.1996.0021
) / Dev Biol by Chen Y (1996) -
M Maden, E Sonneveld, P T van der Saag, E Gale Development (Cambridge, UK) 125, 4133–4144 (1998).
(
10.1242/dev.125.21.4133
) / Development (Cambridge, UK) by Maden M (1998) -
S Izraeli, L A Lowe, V L Bertness, D J Good, D W Dorward, I R Kirsch, M R Kuehn Nature (London) 399, 691–694 (1999).
(
10.1038/21429
) / Nature (London) by Izraeli S (1999) -
E N Meyers, G R Martin Science 285, 403–406 (1999).
(
10.1126/science.285.5426.403
) / Science by Meyers E N (1999) -
C Chazaud, P Chambon, P Dollé Development (Cambridge, UK) 126, 2589–2596 (1999).
(
10.1242/dev.126.12.2589
) / Development (Cambridge, UK) by Chazaud C (1999) -
D P Norris, E J Robertson Genes Dev 13, 1575–1588 (1999).
(
10.1101/gad.13.12.1575
) / Genes Dev by Norris D P (1999) - Rodriguez-Esteban C. Capdevila J. Economides A. N. Pascual J. Ortiz A. & Belmonte J. C. I. (1999) Nature (London) in press.
Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 10:41 a.m.) |
Deposited | 3 years, 2 months ago (June 7, 2022, 12:24 a.m.) |
Indexed | 1 day, 5 hours ago (Aug. 31, 2025, 6:26 a.m.) |
Issued | 25 years, 11 months ago (Sept. 28, 1999) |
Published | 25 years, 11 months ago (Sept. 28, 1999) |
Published Online | 25 years, 11 months ago (Sept. 28, 1999) |
Published Print | 25 years, 11 months ago (Sept. 28, 1999) |
@article{Tsukui_1999, title={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}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.20.11376}, DOI={10.1073/pnas.96.20.11376}, number={20}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Tsukui, Tohru and Capdevila, Javier and Tamura, Koji and Ruiz-Lozano, Pilar and Rodriguez-Esteban, Concepción and Yonei-Tamura, Sayuri and Magallón, Jorge and Chandraratna, Roshantha A. S. and Chien, Kenneth and Blumberg, Bruce and Evans, Ronald M. and Belmonte, Juan Carlos Izpisúa}, year={1999}, month=sep, pages={11376–11381} }