ADMP controls the size of Spemann's organizer through a network of self-regulating expansion-restriction signals
| العنوان: | ADMP controls the size of Spemann's organizer through a network of self-regulating expansion-restriction signals |
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| المؤلفون: | Abraham Fainsod, Hadas Kot-Leibovich, Danny Ben-Zvi, Avi Leibovich |
| المصدر: | BMC Biology BMC Biology, Vol 16, Iss 1, Pp 1-16 (2018) |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, BMP signaling, Physiology, ALK1, Plant Science, Xenopus Proteins, ALK2, Biology, ACVR1, Bone morphogenetic protein, Scaling, General Biochemistry, Genetics and Molecular Biology, Spemann's organizer, dominant negative receptors, Xenopus laevis, 03 medical and health sciences, Structural Biology, Gene expression, Animals, Receptor, lcsh:QH301-705.5, Ecology, Evolution, Behavior and Systematics, Organizers, Embryonic, Embryo, Cell Biology, Transforming growth factor beta, Cell biology, Gastrulation, 030104 developmental biology, lcsh:Biology (General), Bone Morphogenetic Proteins, embryonic structures, biology.protein, General Agricultural and Biological Sciences, Function (biology), Research Article, Xenopus embryos, ADMP, Developmental Biology, Biotechnology |
| الوصف: | Background The bone morphogenetic protein (BMP) signaling gradient is central for dorsoventral patterning in amphibian embryos. This gradient is established through the interaction of several BMPs and BMP antagonists and modulators, some secreted by Spemann's organizer, a cluster of cells coordinating embryonic development. Anti-dorsalizing morphogenetic protein (ADMP), a BMP-like transforming growth factor beta ligand, negatively affects the formation of the organizer, although it is robustly expressed within the organizer itself. Previously, we proposed that this apparent discrepancy may be important for the ability of ADMP to scale the BMP gradient with embryo size, but how this is achieved is unclear. Results Here we report that ADMP acts in the establishment of the organizer via temporally and mechanistically distinct signals. At the onset of gastrulation, ADMP is required to establish normal organizer-specific gene expression domains, thus displaying a dorsal, organizer-promoting function. The organizer-restricting, BMP-like function of ADMP becomes apparent slightly later, from mid-gastrula. The organizer-promoting signal of ADMP is mediated by the activin A type I receptor, ACVR1 (also known as activin receptor-like kinase-2, ALK2). ALK2 is expressed in the organizer and is required for organizer establishment. The anti-organizer function of ADMP is mediated by ACVRL1 (ALK1), a putative ADMP receptor expressed in the lateral regions flanking the organizer that blocks expansion of the organizer. Truncated ALK1 prevents the organizer-restricting effects of ADMP overexpression, suggesting a ligand-receptor interaction. We also present a mathematical model of the regulatory network controlling the size of the organizer. Conclusions We show that the opposed, organizer-promoting and organizer-restricting roles of ADMP are mediated by different receptors. A self-regulating network is proposed in which ADMP functions early through ALK2 to expand its own expression domain, the organizer, and later functions through ALK1 to restrict this domain. These effects are dependent on ADMP concentration, timing, and the spatial localization of the two receptors. This self-regulating temporal switch may control the size of the organizer and the genes expressed within in response to genetic and external stimuli during gastrulation. Electronic supplementary material The online version of this article (10.1186/s12915-018-0483-x) contains supplementary material, which is available to authorized users. |
| تدمد: | 1741-7007 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5d6737ef4008bce6c8a01262bb0d0873Test https://doi.org/10.1186/s12915-018-0483-xTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5d6737ef4008bce6c8a01262bb0d0873 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17417007 |
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