Regulation of nodal and BMP signaling by tomoregulin-1 (X7365) through novel mechanisms
| Autor: | Chang, CB, Eggen, BJL, Weinstein, DC, Brivanlou, AH, Chang, Chenbei, Weinstein, Daniel C., Brivanlou, Ali H. |
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| Přispěvatelé: | Groningen Biomolecular Sciences and Biotechnology, Cell Biochemistry, Molecular Neuroscience and Ageing Research (MOLAR), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE) |
| Rok vydání: | 2003 |
| Předmět: |
Embryo
Nonmammalian XENOPUS FOLLISTATIN Cellular differentiation Xenopus Nodal signaling Xenopus Proteins Mesoderm 0302 clinical medicine Epidermal growth factor Transforming Growth Factor beta Embryonic Induction 0303 health sciences Gene Expression Regulation Developmental NEURAL INDUCTION Cell biology Activins Bone Morphogenetic Proteins embryonic structures DIRECT BINDING hormones hormone substitutes and hormone antagonists Signal Transduction medicine.medical_specialty EXPRESSION CLONING Nodal Protein Recombinant Fusion Proteins SPEMANN ORGANIZER Biology Bone morphogenetic protein EPIDERMAL GROWTH-FACTOR 03 medical and health sciences MESODERM INDUCTION Internal medicine medicine Animals Molecular Biology 030304 developmental biology FOLLISTATIN-RELATED GENE Membrane Proteins Lefty Transforming growth factor beta Gastrula Cell Biology Endocrinology VERTEBRATE DEVELOPMENT TRANSMEMBRANE PROTEIN biology.protein NODAL 030217 neurology & neurosurgery Gene Deletion Follistatin Developmental Biology |
| Zdroj: | Developmental Biology, 255(1), 1-11. ACADEMIC PRESS INC ELSEVIER SCIENCE |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/s0012-1606(02)00075-1 |
| Popis: | During early vertebrate development, members of the transforming growth factor beta (TGFbeta) family play important roles in a variety of processes, including germ layer specification, patterning, cell differentiation, migration, and organogenesis. The activities of TGFbetas need to be tightly controlled to ensure their function at the right time and place. Despite identification of multiple regulators of Bone Morphogenetic Protein (BMP) subfamily ligands, modulators of the activin/nodal class of TGFbeta ligands are limited, and include follistatin, Cerberus, and Lefty. Recently, a membrane protein, tomoregulin-1 (TMEFF1, originally named X7365), was isolated and found to contain two follistatin modules in addition to an Epidermal Growth Factor (EGF) domain, suggesting that TMEFF1 may participate in regulation of TGFbeta function. Here, we show that, unlike follistatin and follistatin-related gene (FLRG), TMEFF1 inhibits nodal but not activin in Xenopus. Interestingly, both the follistatin modules and the EGF motif contribute to nodal inhibition. A soluble protein containing the follistatin and the EGF domains, however, is not sufficient for nodal inhibition; the location of TMEFF1 at the membrane is essential for its function. These results suggest that TMEFF1 inhibits nodal through a novel mechanism. TMEFF1 also blocks mesodermal, but not epidermal induction by BMP2. Unlike nodal inhibition, regulation of BMP activities by TMEFF1 requires the latter's cytoplasmic tail, while deletion of either the follistatin modules or the EGF motif does not interfere with the BMP inhibitory function of TMEFF1. These results imply that TMEFF1 may employ different mechanisms in the regulation of nodal and BMP signals. In Xenopus, TMEFF1 is expressed from midgastrula stages onward and is enriched in neural tissue derivatives. This expression pattern suggests that TMEFF1 may modulate nodal and BMP activities during neural patterning. In summary, our data demonstrate that tomoregulin-1 is a novel regulator of nodal and BMP signaling during early vertebrate embryogenesis. (C) 2003 Elsevier Science (USA). All rights reserved. |
| Databáze: | OpenAIRE |
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