共查询到20条相似文献,搜索用时 15 毫秒
1.
Protein morphogens are instructive signals that regulate growth and patterning of tissues and organs. They form long-range, dynamic gradients by moving from regions of high concentration (producing cells) to regions of low concentration (the adjacent, nonproducing developmental field). Since morphogen activity must be limited to the adjacent target field, we want to understand both how signaling proteins move and how their dispersion is restricted. We consider the variety of settings for long-range morphogen systems in Drosophila. In the early embryo, morphogens appear to disperse by free diffusion, and impermeable membranes physically constrain them. However, at later stages, containment is achieved without physical barriers. We argue that in the absence of constraining barriers, gradient-generating dispersion of morphogens cannot be achieved by passive diffusion and that other mechanisms for distribution must be considered. 相似文献
2.
Bone morphogenetic proteins (BMPs) act as morphogens to control patterning and growth in a variety of developing tissues in different species. How BMP morphogen gradients are established and interpreted in the target tissues has been extensively studied in Drosophila melanogaster. In Drosophila, Decapentaplegic (Dpp), a homologue of vertebrate BMP2/4, acts as a morphogen to control dorsal–ventral patterning of the early embryo and anterior–posterior patterning and growth of the wing imaginal disc. Despite intensive efforts over the last twenty years, how the Dpp morphogen gradient in the wing imaginal disc forms remains controversial, while gradient formation in the early embryo is well understood. In this review, we first focus on the current models of Dpp morphogen gradient formation in these two tissues, and then discuss new strategies using genome engineering and nanobodies to tackle open questions. 相似文献
3.
Mathematical Model of the Formation of Morphogen Gradients Through Membrane-Associated Non-receptors
The importance of morphogens is a central concept in developmental biology. Multiple-fate patterning and the robustness of
the morphogen gradient are essential for embryo development. The ways by which morphogens diffuse from a local source to form
long distance gradients can differ from one morphogen to the other, and for the same morphogen in different organs. This paper
will study the mechanism by which morphogens diffuse through the aid of membrane-associated non-receptors and will investigate
how the membrane-associated non-receptors help the morphogen to form long distance gradients and to achieve good robustness.
Such a mechanism has been reported for some morphogens that are rapidly turned over. We will establish a set of reaction-diffusion
equations to model the dynamical process of morphogen gradient formation. Under the assumption of rapid morphogen degradation,
we discuss the existence, uniqueness, local stability, approximation solution, and the robustness of the steady-state gradient.
The results in this paper show that when the morphogen is rapidly turned over, diffusion of the morphogen through membrane-associated
non-receptors is a possible strategy to form a long distance multiple-fate gradient that is locally stable and is robust against
the changes in morphogen synthesis rate. 相似文献
4.
Few mechanistic ideas from the pre-molecular era of biology have had as enduring an impact as the morphogen concept. In the classical view, cells in developing embryos obtain positional information by measuring morphogen concentrations and comparing them with fixed concentration thresholds; as a result, graded morphogen distributions map into discrete spatial arrangements of gene expression. Recent studies on Hedgehog and other morphogens suggest that establishing patterns of gene expression may be less a function of absolute morphogen concentrations, than of the dynamics of signal transduction, gene expression, and gradient formation. The data point away from any universal model of morphogen interpretation and suggest that organisms use multiple mechanisms for reading out developmental signals in order to accomplish specific patterning goals. 相似文献
5.
Graded signals are an important component of current models of pattern formation. Typically, a group of cells produces a signal that decays as it spreads through neighboring tissue. By contrast with endocrine signals, which spread systemically, patterning signals or morphogens have a restricted zone of influence, an area classically known as a field. The widely accepted model is that graded distribution of such signals allow cells to measure their position relative to the source. Although it provides a framework for understanding pattern formation, the concept of the morphogen raises many mechanistic issues. For example, how the distribution of a morphogen is established and maintained remains an outstanding issue. There is no doubt that signals are transported over distances of tens of cell diameters and that stable gradients do form. The question of how this is achieved has aroused the interest of many cell biologically minded developmental biologists. 相似文献
6.
Morphogen gradients provide long-range positional information by extending across a developing field. To ensure reproducible patterning, their profile is invariable despite genetic or environmental fluctuations. Common models assume a morphogen profile that decays exponentially. Here, we show that exponential profiles cannot, at the same time, buffer fluctuations in morphogen production rate and define long-range gradients. To comply with both requirements, morphogens should decay rapidly close to their source but at a significantly slower rate over most of the field. Numerical search revealed two network designs that support robustness to fluctuations in morphogen production rate. In both cases, morphogens enhance their own degradation, leading to a higher degradation rate close to their source. This is achieved through reciprocal interactions between the morphogen and its receptor. The two robust networks are consistent with properties of the Wg and Hh morphogens in the Drosophila wing disc and provide novel insights into their function. 相似文献
7.
8.
During development, secreted morphogens such as Wnt, Hedgehog (Hh), and BMP emit from their producing cells in a morphogenetic field, and specify different cell fates in a direct concentration-dependent manner. Understanding how morphogens form their concentration gradients to pattern tissues has been a central issue in developmental biology. Various experimental studies from Drosophila have led to several models to explain the formation of morphogen gradients. Over the past decade, one of the main findings in this field is the characterization of heparan sulfate proteoglycan (HSPG) as an essential regulator for morphogen gradient formation. Genetic and cell biological studies have showed that HSPGs can regulate morphogen activities at various steps including control of morphogen movement, signaling, and intracellular trafficking. Here, we review these data, highlighting recent findings that reveal mechanistic roles of HSPGs in controlling morphogen gradient formation.Embryonic development involves many spatial and temporal patterns of cell and tissue organization. These patterning processes are controlled by gradients of morphogens, the “form-generating substances” (Tabata and Takei 2004; Lander 2007). Secreted morphogen molecules, including members of Wnt, Hedgehog (Hh), and transforming growth factor-β (TGF-β) families, are generated from organizing centers and form concentration gradients to specify distinct cell fates in a concentration-dependent manner. Understanding how morphogen gradients are established during development has been a central question in developmental biology. Over the past decade, studies in both Drosophila and vertebrates have yielded important insights in this field. One of the important findings is the characterization of heparan sulfate proteoglycan (HSPG) as an essential regulator for morphogen gradient formation. In this review, we first discuss various models for morphogen movement. Then, we focus on the functions of HSPGs in morphogen movement, signaling, and trafficking. 相似文献
9.
Morphogens are conserved, secreted signalling molecules that regulate the size, shape and patterning of animal tissues and organs. Recent experimental evidence has emphasized the fundamental role of tissue growth in expanding the expression domains of morphogens and their target genes, in generating morphogen gradients and in modulating the response of cells to morphogens. Moreover, the classic view of how morphogens, particularly through their concentration gradient, regulate tissue size during development has been revisited recently. In this review, we discuss how morphogens and tissue growth affect each other, and we attempt to integrate genetic and molecular evidence from vertebrate and invertebrate model systems to put forward the idea that the interaction between growth and morphogens is a general feature of highly proliferative tissues. 相似文献
10.
Gene regulatory logic for reading the Sonic Hedgehog signaling gradient in the vertebrate neural tube 总被引:1,自引:0,他引:1
Balaskas N Ribeiro A Panovska J Dessaud E Sasai N Page KM Briscoe J Ribes V 《Cell》2012,148(1-2):273-284
11.
Erickson JL 《Fly》2011,5(3):266-271
As early as 1964 it was suggested that simple diffusion of morphogens away from their secretion source did not provide an adequate explanation for the formation and maintenance of morphogen gradients. Involvement of the endosome in morphogen distribution models provides an explanation for the slow, directional movement of morphogens, as well as their ability to form intracellular and extracellular gradients independent of morphogen production rates. Drosophila melanogaster morphogens Wg and Dpp form stable, steep, long-range gradients that specify the polarity of the wing disc. The process of endocytosis is imperative to the two central themes in gradient formation: active transport facilitating long-range signaling and degradation of morphogen to sustain gradient shape. This review investigates the endomembrane-mediated processes of re-secretion, degradation and argosome transport of Wg and Dpp in the hope that a better understanding of the endomembrane system will contribute to a more accurate and comprehensive model for morphogen gradient formation and maintenance. 相似文献
12.
Novel brain wiring functions for classical morphogens: a role as graded positional cues in axon guidance 总被引:10,自引:0,他引:10
During embryonic development, morphogens act as graded positional cues to dictate cell fate specification and tissue patterning. Recent findings indicate that morphogen gradients also serve to guide axonal pathfinding during development of the nervous system. These findings challenge our previous notions about morphogens and axon guidance molecules, and suggest that these proteins, rather than having sharply divergent functions, act more globally to provide graded positional information that can be interpreted by responding cells either to specify cell fate or to direct axonal pathfinding. This review presents the roles identified for members of three prominent morphogen families--the Hedgehog, Wnt and TGFbeta/BMP families--in axon guidance, and discusses potential implications for the molecular mechanisms underlying their guidance functions. 相似文献
13.
Signal dynamics in Sonic hedgehog tissue patterning 总被引:3,自引:0,他引:3
14.
Morphogen gradients play a fundamental role in organ patterning and organ growth. Unlike their role in patterning, their function in regulating the growth and the size of organs is poorly understood. How and why do morphogen gradients exert their mitogenic effects to generate uniform proliferation in developing organs, and by what means can morphogens impinge on the final size of organs? The decapentaplegic (Dpp) gradient in the Drosophila wing imaginal disc has emerged as a suitable and established system to study organ growth. Here, we review models and recent findings that attempt to address how the Dpp morphogen contributes to uniform proliferation of cells, and how it may regulate the final size of wing discs. 相似文献
15.
C Tickle 《Seminars in cell & developmental biology》1999,10(3):345-351
The developing limb is an excellent model for pattern formation in vertebrate embryos. Signalling by the polarizing region controls limb pattern across the antero-posterior axis of the chick limb. It was suggested first on theoretical grounds that signalling by the polarizing region could involve a morphogen gradient. Embryological manipulations provided evidence consistent with this model and, more recently, signalling molecules associated with the polarizing region have been identified and tested for their role as morphogens. It is still not clear whether any of the known molecules act directly as a morphogen. The extension of the morphogen model to patterning along the other axes of the limb has been proposed but this may not be applicable. 相似文献
16.
《Fly》2013,7(3):266-271
As early as 1964 it was suggested that simple diffusion of morphogens away from their secretion source did not provide an adequate explanation for the formation and maintenance of morphogen gradients. Involvement of the endosome in morphogen distribution models provides an explanation for the slow, directional movement of morphogens, as well as their abilty to form intracellular and extracellular gradients independent of morphogen production rates. Drosophila melanogaster morphogens Wg and Dpp form stable, steep, long-range gradients that specify the polarity of the wing disc. The process of endocytosis is imparative to the two central themes in gradient formation; active transport facilitating long-range signalling, and degradation of morphogen to sustain gradient shape. This review investigates the endomembrane mediated processes of re-secretion, degradation, and argosome transport of Wg and Dpp in the hope that a better understanding of the endomembrane system will contribute to a more accurate and comprehensive model for morphogen gradient formation and maintenance. 相似文献
17.
Three Drosophila EXT genes shape morphogen gradients through synthesis of heparan sulfate proteoglycans 总被引:5,自引:0,他引:5
The signaling molecules Hedgehog (Hh), Decapentaplegic (Dpp) and Wingless (Wg) function as morphogens and organize wing patterning in Drosophila. In the screen for mutations that alter the morphogen activity, we identified novel mutants of two Drosophila genes, sister of tout-velu (sotv) and brother of tout-velu (botv), and new alleles of tout-velu (ttv). The encoded proteins of these genes belong to an EXT family of proteins that have or are closely related to glycosyltransferase activities required for biosynthesis of heparan sulfate proteoglycans (HSPGs). Mutation in any of these genes impaired biosynthesis of HSPGs in vivo, indicating that, despite their structural similarity, they are not redundant in the HSPG biosynthesis. Protein levels and signaling activities of Hh, Dpp and Wg were reduced in the cells mutant for any of these EXT genes to a various degree, Wg signaling being the least sensitive. Moreover, all three morphogens were accumulated in the front of EXT mutant cells, suggesting that these morphogens require HSPGs to move efficiently. In contrast to previous reports that ttv is involved exclusively in Hh signaling, we found that ttv mutations also affected Dpp and Wg. These data led us to conclude that each of three EXT genes studied contribute to Hh, Dpp and Wg morphogen signaling. We propose that HSPGs facilitate the spreading of morphogens and therefore, function to generate morphogen concentration gradients. 相似文献
18.
The Decapentaplegic morphogen gradient: a precise definition 总被引:2,自引:0,他引:2
Two key processes are in the basis of morphogenesis: the spatial allocation of cell types in fields of na?ve cells and the regulation of growth. Both are controlled by morphogens, which activate target genes in the growing tissue in a concentration-dependent manner. Thus the morphogen model is an intrinsically quantitative concept. However, quantitative studies were performed only in recent years on two morphogens: Bicoid and Decapentaplegic. This review covers quantitative aspects of the formation and precision of the Decapentaplegic morphogen gradient. The morphogen gradient concept is transitioning from a soft definition to a precise idea of what the gradient could really do. 相似文献
19.
Quantitative data from the Drosophila wing imaginal disc reveals that the amplitude of the Decapentaplegic (Dpp) morphogen gradient increases continuously. It is an open question how cells can determine their relative position within a domain based on a continuously increasing gradient. Here we show that pre-steady state diffusion-based dispersal of morphogens results in a zone within the growing domain where the concentration remains constant over the patterning period. The position of the zone that is predicted based on quantitative data for the Dpp morphogen corresponds to where the Dpp-dependent gene expression boundaries of spalt (sal) and daughters against dpp (dad) emerge. The model also suggests that genes that are scaling and are expressed at lateral positions are either under the control of a different read-out mechanism or under the control of a different morphogen. The patterning mechanism explains the extraordinary robustness that is observed for variations in Dpp production, and offers an explanation for the dual role of Dpp in controlling patterning and growth. Pre-steady-state dynamics are pervasive in morphogen-controlled systems, thus making this a probable general mechanism for the scaled read-out of morphogen gradients in growing developmental systems. 相似文献
20.
The amphibian embryo provides a powerful model system to study morphogen gradients because of the ease with which it is possible to manipulate the early embryo. In particular, it is possible to introduce exogenous sources of morphogen, to follow the progression of the signal, to monitor the cellular response to induction, and to up- or down-regulate molecules that are involved in all aspects of long-range signaling. In this article, I discuss the evidence that gradients exist in the early amphibian embryo, the way in which morphogens might traverse a field of cells, and the way in which different concentrations of morphogens might be interpreted to activate the expression of different genes.The idea that a morphogen gradient activates the expression of different genes at different concentrations was perhaps stated most clearly by Wolpert''s French flag model, in which a graded signal activates the expression of “blue,” “white,” and “red” genes at high, intermediate, and low concentrations (Wolpert 1969). Since that original work, great progress has been made in identifying morphogens and their target genes and it is now clear that the spatial pattern of gene expression in the developing embryo is frequently established by graded signals of this sort. But many questions remain, and in particular little is known about how gradients are established in the embryo with the necessary precision and how cells interpret different concentrations of morphogen to activate different genes. I discuss these issues with respect to mesoderm induction in the developing amphibian embryo. 相似文献