Twisted gastrulation loss-of-function analyses support its role as a BMP inhibitor during earlyXenopusembryogenesis
Author:
Blitz Ira L.1, Cho Ken W. Y.1, Chang Chenbei2
Affiliation:
1. Department of Developmental and Cell Biology, and the Developmental Biology Center, 4213 McGaugh Hall, University of California, Irvine, CA 92697-2300,USA 2. Department of Cell Biology, 360 McCallum Building, 1530 3rd Avenue South,University of Alabama, Birmingham, AL 35294-0005, USA
Abstract
BMP signals play important roles in the regulation of diverse events in development and in the adult. In amniotes, like the amphibian Xenopus laevis, BMPs promote ventral specification, while chordin and other BMP inhibitors expressed dorsally in the Spemann's organizer play roles in establishment and/or maintenance of this region as dorsal endomesoderm. The activities of chordin are in turn regulated by the secreted proteolytic enzymes BMP1 and Xolloid. Recently, we and others have identified the protein twisted gastrulation (TSG) as a soluble BMP modulator that functions by modifying chordin activity. Overexpression and genetic analyses in Drosophila, Xenopus and zebrafish together with in vitro biochemical studies suggest that TSG might act as a BMP antagonist; but there is also evidence that TSG may promote BMP signaling. Here we report examination of the in vivo function of TSG in early Xenopusdevelopment using a loss-of-function approach. We show that reducing TSG expression using antisense TSG morpholino oligonucleotides (MOs) results in moderate head defects. These defects can be rescued both by a TSG that cannot be inhibited by the MO, and by the BMP antagonists chordin and noggin. Furthermore, while neither the onset of gastrulation nor the expression of marker genes are affected in early gastrulae, dorsal marker gene expression is reduced at the expense of expanded ventral marker gene expression beginning at mid to late gastrula stage. TSG-MO and Chd-MOs also cooperate to strongly repress head formation. Finally, we note that the loss of TSG function results in a shift in tissue responsiveness to the BMP inhibitory function of chordin in both animal caps and the ventral marginal zone, a result that implies that the activity of TSG may be required for chordin to efficiently inhibit BMPs in these developmental contexts. These data, taken together with the biochemistry and overexpression studies, argue that TSG plays an important role in regulating the potency of chordin's BMP inhibitory activity and TSG and chordin act together to regulate the extent of dorsoanterior development of early frog embryos.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference63 articles.
1. Arora, K. and Nusslein-Volhard, C. (1992). Altered mitotic domains reveal fate map changes in Drosophila embryos mutant for zygotic dorsoventral patterning genes. Development114,1003-1024. 2. Bachiller, D., Klingensmith, J., Kemp, C., Belo, J. A.,Anderson, R. M., May, S. R., McMahon, J. A., McMahon, A. P., Harland,R. M., Rossant, J. and de Robertis, E. M. (2000). The organizer factors Chordin and Noggin are required for mouse forebrain development. Nature403,658-661. 3. Blitz, I. L. and Cho, K. W. (1995). Anterior neurectoderm is progressively induced during gastrulation: the role of the Xenopus homeobox gene orthodenticle. Development121,993-1004. 4. Blitz, I. L., Shimmi, O., Wunnenberg-Stapleton, K., O'Connor, M. B. and Cho, K. W. (2000). Is chordin a long-range- or short-range-acting factor? Roles for BMP1-related metalloproteases in chordin and BMP4 autofeedback loop regulation. Dev. Biol.223,120-138. 5. Blumberg, B., Wright, C. V., de Robertis, E. M. and Cho, K. W. Y. (1991). Organizer-specific homeobox genes in Xenopus laevis embryos. Science253,194-196.
Cited by
46 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|