|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
Development, Vol 128, Issue 10 1831-1843, Copyright © 2001 by Company of Biologists
JOURNAL ARTICLES |
LA Lowe, S Yamada and MR Kuehn
Experimental Immunology Branch, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. mkuehn@mail.nih.gov
Loss-of-function analysis has shown that the transforming growth factor-like signaling molecule nodal is essential for mouse mesoderm development. However, definitive proof of nodal function in other developmental processes in the mouse embryo has been lacking because the null mutation blocks gastrulation. We describe the generation and analysis of a hypomorphic nodal allele. Mouse embryos heterozygous for the hypomorphic allele and a null allele undergo gastrulation but then display abnormalities that fall into three distinct mutant phenotypic classes, which may result from expression levels falling below critical thresholds in one or more domains of nodal expression. Our analysis of each of these classes provides conclusive evidence for nodal-mediated regulation of several developmental processes in the mouse embryo, beyond its role in mesoderm formation. We find that nodal signaling is required for correct positioning of the anteroposterior axis, normal anterior and midline patterning, and the left-right asymmetric development of the heart, vasculature, lungs and stomach.
This article has been cited by other articles:
|
|
 |
|
  D. C. Hay, J. Fletcher, C. Payne, J. D. Terrace, R. C. J. Gallagher, J. Snoeys, J. R. Black, D. Wojtacha, K. Samuel, Z. Hannoun, et al. Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling PNAS, August 26, 2008; 105(34): 12301 - 12306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Agarwal, K. L. Holton, and R. Lanza Efficient Differentiation of Functional Hepatocytes from Human Embryonic Stem Cells Stem Cells, May 1, 2008; 26(5): 1117 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Shiraki, T. Yoshida, K. Araki, A. Umezawa, Y. Higuchi, H. Goto, K. Kume, and S. Kume Guided Differentiation of Embryonic Stem Cells into Pdx1-Expressing Regional-Specific Definitive Endoderm Stem Cells, April 1, 2008; 26(4): 874 - 885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D'Andrea, G. L. Liguori, J. A. Le Good, E. Lonardo, O. Andersson, D. B. Constam, M. G. Persico, and G. Minchiotti Cripto promotes A-P axis specification independently of its stimulatory effect on Nodal autoinduction J. Cell Biol., February 6, 2008; 180(3): 597 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Shen Nodal signaling: developmental roles and regulation Development, March 15, 2007; 134(6): 1023 - 1034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. McLean, K. A. D'Amour, K. L. Jones, M. Krishnamoorthy, M. J. Kulik, D. M. Reynolds, A. M. Sheppard, H. Liu, Y. Xu, E. E. Baetge, et al. Activin A Efficiently Specifies Definitive Endoderm from Human Embryonic Stem Cells Only When Phosphatidylinositol 3-Kinase Signaling Is Suppressed Stem Cells, January 1, 2007; 25(1): 29 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Kuang, Y. Xiao, L. Yang, Q. Chen, Z. Wang, S. J. Conway, and Y. Chen Intragenic deletion of Tgif causes defectsin brain development Hum. Mol. Genet., December 15, 2006; 15(24): 3508 - 3519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Gadue, T. L. Huber, P. J. Paddison, and G. M. Keller Wnt and TGF-beta signaling are required for the induction of an in vitro model of primitive streak formation using embryonic stem cells PNAS, November 7, 2006; 103(45): 16806 - 16811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. V. Cardoso and J. Lu Regulation of early lung morphogenesis: questions, facts and controversies Development, May 1, 2006; 133(9): 1611 - 1624. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Rippon, J. M. Polak, M. Qin, and A. E. Bishop Derivation of Distal Lung Epithelial Progenitors from Murine Embryonic Stem Cells Using a Novel Three-Step Differentiation Protocol Stem Cells, May 1, 2006; 24(5): 1389 - 1398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Jeong, K. El-Jaick, E. Roessler, M. Muenke, and D. J. Epstein A functional screen for sonic hedgehog regulatory elements across a 1 Mb interval identifies long-range ventral forebrain enhancers Development, February 15, 2006; 133(4): 761 - 772. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Chen, S. M. Ware, A. Sato, D. E. Houston-Hawkins, R. Habas, M. M. Matzuk, M. M. Shen, and C. W. Brown The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo Development, January 15, 2006; 133(2): 319 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chu, J. Ding, K. Jeays-Ward, S. M. Price, M. Placzek, and M. M. Shen Non-cell-autonomous role for Cripto in axial midline formation during vertebrate embryogenesis Development, December 15, 2005; 132(24): 5539 - 5551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Houston and C. Wylie Maternal Xenopus Zic2 negatively regulates Nodal-related gene expression during anteroposterior patterning Development, November 1, 2005; 132(21): 4845 - 4855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tada, T. Era, C. Furusawa, H. Sakurai, S. Nishikawa, M. Kinoshita, K. Nakao, T. Chiba, and S.-I. Nishikawa Characterization of mesendoderm: a diverging point of the definitive endoderm and mesoderm in embryonic stem cell differentiation culture Development, October 1, 2005; 132(19): 4363 - 4374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Gotoh, K. Manova, S. Tanaka, M. Murohashi, Y. Hadari, A. Lee, Y. Hamada, T. Hiroe, M. Ito, T. Kurihara, et al. The Docking Protein FRS2{alpha} Is an Essential Component of Multiple Fibroblast Growth Factor Responses during Early Mouse Development Mol. Cell. Biol., May 15, 2005; 25(10): 4105 - 4116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jornvall, E. Reissmann, O. Andersson, M. Mehrkash, and C. F. Ibanez ALK7, a Receptor for Nodal, Is Dispensable for Embryogenesis and Left-Right Patterning in the Mouse Mol. Cell. Biol., November 1, 2004; 24(21): 9383 - 9389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. Chu, N. R. Dunn, D. C. Anderson, L. Oxburgh, and E. J. Robertson Differential requirements for Smad4 in TGF{beta}-dependent patterning of the early mouse embryo Development, August 1, 2004; 131(15): 3501 - 3512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bonnafe, M. Touka, A. AitLounis, D. Baas, E. Barras, C. Ucla, A. Moreau, F. Flamant, R. Dubruille, P. Couble, et al. The Transcription Factor RFX3 Directs Nodal Cilium Development and Left-Right Asymmetry Specification Mol. Cell. Biol., May 15, 2004; 24(10): 4417 - 4427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Dunn, S. D. Vincent, L. Oxburgh, E. J. Robertson, and E. K. Bikoff Combinatorial activities of Smad2 and Smad3 regulate mesoderm formation and patterning in the mouse embryo Development, April 15, 2004; 131(8): 1717 - 1728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kubo, K. Shinozaki, J. M. Shannon, V. Kouskoff, M. Kennedy, S. Woo, H. J. Fehling, and G. Keller Development of definitive endoderm from embryonic stem cells in culture Development, April 1, 2004; 131(7): 1651 - 1662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W. Harms and C. Chang Tomoregulin-1 (TMEFF1) inhibits nodal signaling through direct binding to the nodal coreceptor Cripto Genes & Dev., November 1, 2003; 17(21): 2624 - 2629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Trinh, D. Meyer, and D. Y. R. Stainier The Mix family homeodomain gene bonnie and clyde functions with other components of the Nodal signaling pathway to regulate neural patterning in zebrafish Development, October 15, 2003; 130(20): 4989 - 4998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tian, C. Yam, G. Balasundaram, H. Wang, A. Gore, and K. Sampath A temperature-sensitive mutation in the nodal-related gene cyclops reveals that the floor plate is induced during gastrulation in zebrafish Development, July 15, 2003; 130(14): 3331 - 3342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. TAYLOR, W. J. M. VAN DE VEN, and J. W. M. CREEMERS Curbing activation: proprotein convertases in homeostasis and pathology FASEB J, July 1, 2003; 17(10): 1215 - 1227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Vincent, N. R. Dunn, S. Hayashi, D. P. Norris, and E. J. Robertson Cell fate decisions within the mouse organizer are governed by graded Nodal signals Genes & Dev., July 1, 2003; 17(13): 1646 - 1662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Long, N. Ahmad, and M. Rebagliati The zebrafish nodal-related gene southpaw is required for visceral and diencephalic left-right asymmetry Development, June 1, 2003; 130(11): 2303 - 2316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yamamoto, N. Mine, K. Mochida, Y. Sakai, Y. Saijoh, C. Meno, and H. Hamada Nodal signaling induces the midline barrier by activating Nodal expression in the lateral plate Development, May 1, 2003; 130(9): 1795 - 1804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sachinidis, B. K. Fleischmann, E. Kolossov, M. Wartenberg, H. Sauer, and J. Hescheler Cardiac specific differentiation of mouse embryonic stem cells Cardiovasc Res, May 1, 2003; 58(2): 278 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Fujiwara, D. B. Dehart, K. K. Sulik, and B. L. M. Hogan Distinct requirements for extra-embryonic and embryonic bone morphogenetic protein 4 in the formation of the node and primitive streak and coordination of left-right asymmetry in the mouse Development, March 12, 2003; 129(20): 4685 - 4696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Piedra and M. A. Ros BMP signaling positively regulates Nodal expression during left right specification in the chick embryo Development, March 9, 2003; 129(14): 3431 - 3440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Norris, J. Brennan, E. K. Bikoff, and E. J. Robertson The Foxh1-dependent autoregulatory enhancer controls the level of Nodal signals in the mouse embryo Development, March 9, 2003; 129(14): 3455 - 3468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. H. Przemeck, U. Heinzmann, J. Beckers, and M. Hrabe de Angelis Node and midline defects are associated with left-right development in Delta1 mutant embryos Development, January 1, 2003; 130(1): 3 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Cheng, F. Olale, J. T. Bennett, A. H. Brivanlou, and A. F. Schier EGF-CFC proteins are essential coreceptors for the TGF-beta signals Vg1 and GDF1 Genes & Dev., January 1, 2003; 17(1): 31 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Oh, C.-Y. Yeo, Y. Lee, H. Schrewe, M. Whitman, and E. Li Activin type IIA and IIB receptors mediate Gdf11 signaling in axial vertebral patterning Genes & Dev., November 1, 2002; 16(21): 2749 - 2754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Y.R. Stainier A glimpse into the molecular entrails of endoderm formation Genes & Dev., April 15, 2002; 16(8): 893 - 907. [Full Text] [PDF]
|
|
