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

First published online 20 April 2005
doi: 10.1242/dev.01822

This Article Figures Only Full Text Full Text (PDF) Supplementary Material OA All Versions of this Article: dev.01822v1 132/10/2489    most recent 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 Zakin, L. Articles by De Robertis, E. M. Search for Related Content PubMed PubMed Citation Articles by Zakin, L. Articles by De Robertis, E. M.

Sirenomelia in Bmp7 and Tsg compound mutant mice: requirement for Bmp signaling in the development of ventral posterior mesoderm

¹ Howard Hughes Medical Institute, and Department of Biological Chemistry, University of California, Los Angeles, CA 90095-1662, USA
² Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095, USA

^* Author for correspondence (e-mail: derobert{at}mednet.ucla.edu)

Accepted 21 March 2005

Sirenomelia or mermaid-like phenotype is one of the principal human congenital malformations that can be traced back to the stage of gastrulation. Sirenomelia is characterized by the fusion of the two hindlimbs into a single one. In the mouse, sirens have been observed in crosses between specific strains and as the consequence of mutations that increase retinoic acid levels. We report that the loss of bone morphogenetic protein 7 (Bmp7) in combination with a half dose or complete loss of twisted gastrulation (Tsg) causes sirenomelia in the mouse. Tsg is a Bmp- and chordin-binding protein that has multiple effects on Bmp metabolism in the extracellular space; Bmp7 is one of many Bmps and is shown here to bind to Tsg. In Xenopus, co-injection of Tsg and Bmp7 morpholino oligonucleotides (MO) has a synergistic effect, greatly inhibiting formation of ventral mesoderm and ventral fin tissue. In the mouse, molecular marker studies indicate that the sirenomelia phenotype is associated with a defect in the formation of ventroposterior mesoderm. These experiments demonstrate that dorsoventral patterning of the mouse posterior mesoderm is regulated by Bmp signaling, as is the case in other vertebrates. Sirens result from a fusion of the hindlimb buds caused by a defect in the formation of ventral mesoderm.

Key words: Sirenomelia, Twisted gastrulation (Twsg1), Bmp, Bmp4, Morpholino, Limb bud, TGFß, Chordin, Dorsoventral patterning, Mouse, Xenopus

This article has been cited by other articles:

				S. Ohta, K. Suzuki, K. Tachibana, H. Tanaka, and G. Yamada Cessation of gastrulation is mediated by suppression of epithelial-mesenchymal transition at the ventral ectodermal ridge Development, December 15, 2007; 134(24): 4315 - 4324. [Abstract] [Full Text] [PDF]

				M. Ikeya, M. Kawada, H. Kiyonari, N. Sasai, K. Nakao, Y. Furuta, and Y. Sasai Essential pro-Bmp roles of crossveinless 2 in mouse organogenesis Development, November 15, 2006; 133(22): 4463 - 4473. [Abstract] [Full Text] [PDF]

				M. Schmidl, N. Adam, C. Surmann-Schmitt, T. Hattori, M. Stock, U. Dietz, B. de Crombrugghe, E. Poschl, and K. von der Mark Twisted Gastrulation Modulates Bone Morphogenetic Protein-induced Collagen II and X Expression in Chondrocytes in Vitro and in Vivo J. Biol. Chem., October 20, 2006; 281(42): 31790 - 31800. [Abstract] [Full Text] [PDF]

				U. J. Pyati, M. S. Cooper, A. J. Davidson, A. Nechiporuk, and D. Kimelman Sustained Bmp signaling is essential for cloaca development in zebrafish Development, June 1, 2006; 133(11): 2275 - 2284. [Abstract] [Full Text] [PDF]

				B. Reversade, H. Kuroda, H. Lee, A. Mays, and E. M. De Robertis Depletion of Bmp2, Bmp4, Bmp7 and Spemann organizer signals induces massive brain formation in Xenopus embryos Development, August 1, 2005; 132(15): 3381 - 3392. [Abstract] [Full Text] [PDF]