Fine-tuned shuttles for bone morphogenetic proteins

Wharton, Kristi A.; Serpe, Mihaela

doi:10.1016/j.gde.2013.04.012

Cited by 25 publications

(41 citation statements)

References 97 publications

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“…In the embryo, an orchestra of ligand binding proteins, proteases, and surface proteins are required to form a sharp dorsal stripe of Dpp. In the wing disc, a gradient that scales with the growing tissue requires a network of positive and negative feedback loops [6]. Dpp signaling is also critical for germ cell proliferation and renewal in the ovary and testis.…”

Section: Ligandsmentioning

confidence: 99%

“…Accessory factors have been identified that support ligand-receptor binding, such as the so-called mammalian Type III TGF-β receptor [5]. Several types of “co-receptors” for BMP signaling have been suggested including Dally and Dally-like, two Drosophila glipican homologs, and CV-2, a BMP binding protein that can associate with Punt in some circumstances to facilitate Dpp signaling [6]. The requirement for additional cofactors in Drosophila can also be inferred from contrasting cell culture and in vivo data.…”

Section: Receptorsmentioning

confidence: 99%

“…In many cases using model organisms has helped identify not only the major players for modulation of TGF-β signaling activity but also their molecular activities. The best examples of this to date are the study of BMP morphogen gradients and movement of signaling molecules [5–6]. Facilitated diffusion of Dpp in the early embryo is one of the classic cases of morphogen action pattern changing over developmental time.…”

Section: Introduction: An Ancient Signaling Pathwaymentioning

confidence: 99%

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Strategies for exploring TGF-β signaling in Drosophila

Peterson

O’Connor

2014

Methods

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The TGF-beta pathway is an evolutionarily conserved signal transduction module that mediates diverse biological processes in animals. In Drosophila, both the BMP and Activin branches are required for viability. Studies rooted in classical and molecular genetic approaches continue to uncover new developmental roles for TGF-beta signaling. We present an overview of the secreted ligands, transmembrane receptors and cellular Smad transducer proteins that comprise the core pathway in Drosophila. An assortment of tools have been developed to conduct tissue-specific loss and gain-of-function experiments for these pathway components. We discuss the deployment of these reagents, with an emphasis on appropriate usage and limitations of the available tools. Throughout, we note reagents that are in need of further improvement of development, and signaling features requiring further study. A general theme is that comparison of phenotypes for ligands, receptors, and Smads can be used to map tissue interactions, and to separate canonical and non-canonical signaling activities. Core TGF-beta signaling components are subject to multiple layers of regulation, and are coupled to context-specific inputs and outputs. In addition to fleshing out how TGF-beta signaling serves the fruit fly, we anticipate that future studies will uncover new regulatory nodes and modes and will continue to advance paradigms for how TGF-beta signaling regulates general developmental processes.

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Section: Ligandsmentioning

confidence: 99%

Section: Receptorsmentioning

confidence: 99%

Section: Introduction: An Ancient Signaling Pathwaymentioning

confidence: 99%

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Strategies for exploring TGF-β signaling in Drosophila

Peterson

O’Connor

2014

Methods

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“…Binding of twisted gastrulation (Tsg) to BMP‐Sog complexes thereby results in their specific release from collagen IV . By doing so, Tsg enhances Sog/Chordin binding to BMPs and thus enhances BMP mobility, whereas BMP1 family metalloproteases regulate complex disruption by Sog/Chordin cleavage and liberation of bioactive ligands .…”

Section: Regulation Of Bmp Signalingmentioning

confidence: 99%

BMP growth factor signaling in a biomechanical context

et al. 2013

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Bone Morphogenetic Proteins (BMPs) are members of the transforming growth factor-β superfamily of secreted polypeptide growth factors and are important regulators in a multitude of cellular processes. To ensure the precise and balanced propagation of their pleiotropic signaling responses, BMPs and their corresponding signaling pathways are subject to tight control. A large variety of regulatory mechanisms throughout different biological levels combines into a complex network and provides the basis for physiological BMP function. This regulatory network not only includes biochemical factors but also mechanical cues. Both BMP signaling and mechanotransduction pathways are tightly interconnected and represent an elaborate signaling network active during development but also during organ homeostasis. Moreover, its dysregulation is associated with a number of human pathologies. A more detailed understanding of this crosstalk in respect to molecular interactions will be indispensable in the future, in particular to understand BMP-related diseases as well as with regard to an efficient clinical application of BMP ligands.

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“…In Drosophila melanogaster embryos, the BMP gradient forms through directed extracellular BMP movement and initiates a positive feedback circuit leading to a bistable pattern of BMP signaling by the end of the blastoderm stage (reviewed in O'Connor et al, 2006; Shilo et al, 2013; Wharton and Serpe, 2013). High levels of BMP signaling, centered on the dorsal midline, specify a single extraembryonic tissue, the amnioserosa.…”

Section: Introductionmentioning

confidence: 99%

Functional evolution of a morphogenetic gradient

Kwan

Gavin-Smyth

Ferguson

et al. 2016

eLife

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Bone Morphogenetic Proteins (BMPs) pattern the dorsal-ventral axis of bilaterian embryos; however, their roles in the evolution of body plan are largely unknown. We examined their functional evolution in fly embryos. BMP signaling specifies two extraembryonic tissues, the serosa and amnion, in basal-branching flies such as Megaselia abdita, but only one, the amnioserosa, in Drosophila melanogaster. The BMP signaling dynamics are similar in both species until the beginning of gastrulation, when BMP signaling broadens and intensifies at the edge of the germ rudiment in Megaselia, while remaining static in Drosophila. Here we show that the differences in gradient dynamics and tissue specification result from evolutionary changes in the gene regulatory network that controls the activity of a positive feedback circuit on BMP signaling, involving the tumor necrosis factor alpha homolog eiger. These data illustrate an evolutionary mechanism by which spatiotemporal changes in morphogen gradients can guide tissue complexity.DOI: http://dx.doi.org/10.7554/eLife.20894.001

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Fine-tuned shuttles for bone morphogenetic proteins

Cited by 25 publications

References 97 publications

Strategies for exploring TGF-β signaling in Drosophila

Strategies for exploring TGF-β signaling in Drosophila

BMP growth factor signaling in a biomechanical context

Functional evolution of a morphogenetic gradient

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