QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tremblay, K. D. Articles by Robertson, E. J. Search for Related Content PubMed PubMed Citation Articles by Tremblay, K. D. Articles by Robertson, E. J.

Mouse embryos lacking Smad1 signals display defects in extra-embryonic tissues and germ cell formation

Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA

*Author for correspondence (e-mail: ejrobert{at}fas.harvard.edu)

Accepted June 21, 2001

The Smad proteins are important intracellular mediators of the transforming growth factor ß (TGFß) family of secreted growth factors. Smad1 is an effector of signals provided by the bone morphogenetic protein (BMP) sub-group of TGFß molecules. To understand the role of Smad1 in mouse development, we have generated a Smad1 loss-of-function allele using homologous recombination in ES cells. Smad1-/- embryos die by 10.5 dpc because they fail to connect to the placenta. Mutant embryos are first recognizable by 7.0 dpc, owing to a characteristic localized outpocketing of the visceral endoderm at the posterior embryonic/extra-embryonic junction, accompanied by a dramatic twisting of the epiblast and nascent mesoderm. Chimera analysis reveals that these two defects are attributable to a requirement for Smad1 in the extra-embryonic tissues. By 7.5 dpc, Smad1-deficient embryos show a marked impairment in allantois formation. By contrast, the chorion overproliferates, is erratically folded within the extra-embryonic space and is impeded in proximal migration. BMP signals are known to be essential for the specification and proliferation of primordial germ cells. We find a drastic reduction of primordial germ cells in Smad1-deficient embryos, suggesting an essential role for Smad1-dependent signals in primordial germ cell specification. Surprisingly, despite the key involvement of BMP signaling in tissues of the embryo proper, Smad1-deficient embryos develop remarkably normally. An examination of the expression domains of Smad1, Smad5 and Smad8 in early mouse embryos show that, while Smad1 is uniquely expressed in the visceral endoderm at 6.5 dpc, in other tissues Smad1 is co-expressed with Smad5 and/or Smad8. Collectively, these data have uncovered a unique function for Smad1 signaling in coordinating the growth of extra-embryonic structures necessary to support development within the uterine environment.

Key words: Smad1, Extra-embryonic tissues, Primordial germ cells, BMP, Mouse

This article has been cited by other articles:

				K. Kurimoto, Y. Yabuta, Y. Ohinata, M. Shigeta, K. Yamanaka, and M. Saitou Complex genome-wide transcription dynamics orchestrated by Blimp1 for the specification of the germ cell lineage in mice Genes & Dev., June 15, 2008; 22(12): 1617 - 1635. [Abstract] [Full Text] [PDF]

				M. Saura, C. Zaragoza, B. Herranz, M. Griera, L. Diez-Marques, D. Rodriguez-Puyol, and M. Rodriguez-Puyol Nitric Oxide Regulates Transforming Growth Factor-{beta} Signaling in Endothelial Cells Circ. Res., November 25, 2005; 97(11): 1115 - 1123. [Abstract] [Full Text] [PDF]

				K.-H. Yew, M. Hembree, K. Prasadan, B. Preuett, C. McFall, C. Benjes, A. Crowley, S. Sharp, S. Tulachan, S. Mehta, et al. Cross-talk between Bone Morphogenetic Protein and Transforming Growth Factor-{beta} Signaling Is Essential for Exendin-4-induced Insulin-positive Differentiation of AR42J Cells J. Biol. Chem., September 16, 2005; 280(37): 32209 - 32217. [Abstract] [Full Text] [PDF]

				C. Chen, H. Chen, J. Sun, P. Bringas Jr., Y. Chen, D. Warburton, and W. Shi Smad1 expression and function during mouse embryonic lung branching morphogenesis Am J Physiol Lung Cell Mol Physiol, June 1, 2005; 288(6): L1033 - L1039. [Abstract] [Full Text] [PDF]

				M. Masaki, M. Izumi, Y. Oshima, Y. Nakaoka, T. Kuroda, R. Kimura, S. Sugiyama, K. Terai, M. Kitakaze, K. Yamauchi-Takihara, et al. Smad1 Protects Cardiomyocytes From Ischemia-Reperfusion Injury Circulation, May 31, 2005; 111(21): 2752 - 2759. [Abstract] [Full Text] [PDF]

				K. L. Abrams, J. Xu, C. Nativelle-Serpentini, S. Dabirshahsahebi, and M. B. Rogers An Evolutionary and Molecular Analysis of Bmp2 Expression J. Biol. Chem., April 16, 2004; 279(16): 15916 - 15928. [Abstract] [Full Text] [PDF]

				P. Vrljicak, D. Myburgh, A. K. Ryan, M. A. van Rooijen, C. L. Mummery, and I. R. Gupta Smad expression during kidney development Am J Physiol Renal Physiol, April 1, 2004; 286(4): F625 - F633. [Abstract] [Full Text] [PDF]

				C. A. Adelman, S. Chattopadhyay, and J. J. Bieker The BMP/BMPR/Smad pathway directs expression of the erythroid-specific EKLF and GATA1 transcription factors during embryoid body differentiation in serum-free media Development, March 3, 2003; 129(2): 539 - 549. [Abstract] [Full Text] [PDF]

				C. Angley, M. Kumar, K. J. Dinsio, A. K. Hall, and R. E. Siegel Signaling by Bone Morphogenetic Proteins and Smad1 Modulates the Postnatal Differentiation of Cerebellar Cells J. Neurosci., January 1, 2003; 23(1): 260 - 268. [Abstract] [Full Text] [PDF]

				H. Chang, C. W. Brown, and M. M. Matzuk Genetic Analysis of the Mammalian Transforming Growth Factor-{beta} Superfamily Endocr. Rev., December 1, 2002; 23(6): 787 - 823. [Abstract] [Full Text] [PDF]

				A. I. Agoulnik, B. Lu, Q. Zhu, C. Truong, M. T. Ty, N. Arango, K. K. Chada, and C. E. Bishop A novel gene, Pog, is necessary for primordial germ cell proliferation in the mouse and underlies the germ cell deficient mutation, gcd Hum. Mol. Genet., November 15, 2002; 11(24): 3047 - 3053. [Abstract] [Full Text] [PDF]

				G. Valdimarsdottir, M.-J. Goumans, A. Rosendahl, M. Brugman, S. Itoh, F. Lebrin, P. Sideras, and P. ten Dijke Stimulation of Id1 Expression by Bone Morphogenetic Protein Is Sufficient and Necessary for Bone Morphogenetic Protein-Induced Activation of Endothelial Cells Circulation, October 22, 2002; 106(17): 2263 - 2270. [Abstract] [Full Text] [PDF]

				Y. Miyanaga, I. Torregroza, and T. Evans A Maternal Smad Protein Regulates Early Embryonic Apoptosis in Xenopus laevis Mol. Cell. Biol., March 1, 2002; 22(5): 1317 - 1328. [Abstract] [Full Text] [PDF]

				T. Fujiwara, N. R. Dunn, and B. L. M. Hogan Bone morphogenetic protein 4 in the extraembryonic mesoderm is required for allantois development and the localization and survival of primordial germ cells in the mouse PNAS, November 9, 2001; (2001) 241508898. [Abstract] [Full Text] [PDF]

				T. Fujiwara, N. R. Dunn, and B. L. M. Hogan Bone morphogenetic protein 4 in the extraembryonic mesoderm is required for allantois development and the localization and survival of primordial germ cells in the mouse PNAS, November 20, 2001; 98(24): 13739 - 13744. [Abstract] [Full Text] [PDF]