The Experts below are selected from a list of 22032 Experts worldwide ranked by ideXlab platform
Peter W Reddien - One of the best experts on this subject based on the ideXlab platform.
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activin-2 is required for regeneration of polarity on the planarian anterior-posterior axis.
PLoS genetics, 2021Co-Authors: Jennifer K Cloutier, Conor L Mcmann, Isaac M Oderberg, Peter W ReddienAbstract:Planarians are flatworms and can perform whole-body regeneration. This ability involves a mechanism to distinguish between anterior-facing wounds that require head regeneration and posterior-facing wounds that require tail regeneration. How this head-tail regeneration polarity decision is made is studied to identify principles underlying tissue-identity specification in regeneration. We report that inhibition of activin-2, which encodes an Activin-like signaling ligand, resulted in the regeneration of ectopic posterior-facing heads following amputation. During tissue turnover in uninjured planarians, Positional Information is constitutively expressed in muscle to maintain proper patterning. Positional Information includes Wnts expressed in the posterior and Wnt antagonists expressed in the anterior. Upon amputation, several wound-induced genes promote re-establishment of Positional Information. The head-versus-tail regeneration decision involves preferential wound induction of the Wnt antagonist notum at anterior-facing over posterior-facing wounds. Asymmetric activation of notum represents the earliest known molecular distinction between head and tail regeneration, yet how it occurs is unknown. activin-2 RNAi animals displayed symmetric wound-induced activation of notum at anterior- and posterior-facing wounds, providing a molecular explanation for their ectopic posterior-head phenotype. activin-2 RNAi animals also displayed anterior-posterior (AP) axis splitting, with two heads appearing in anterior blastemas, and various combinations of heads and tails appearing in posterior blastemas. This was associated with ectopic nucleation of anterior poles, which are head-tip muscle cells that facilitate AP and medial-lateral (ML) pattern, at posterior-facing wounds. These findings reveal a role for Activin signaling in determining the outcome of AP-axis-patterning events that are specific to regeneration.
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Muscle functions as a connective tissue and source of extracellular matrix in planarians
Nature Publishing Group, 2019Co-Authors: Lauren E. Cote, Eric Simental, Peter W ReddienAbstract:How the cellular source of Positional Information compares across regenerative animals is unclear. Here, the authors find that planarian muscle, which harbours Positional Information, acts as a connective tissue by being a major site of matrisome gene expression and by maintaining tissue architecture
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the cellular and molecular basis for planarian regeneration
Cell, 2018Co-Authors: Peter W ReddienAbstract:Regeneration is one of the great mysteries of biology. Planarians are flatworms capable of dramatic feats of regeneration, which have been studied for over 2 centuries. Recent findings identify key cellular and molecular principles underlying these feats. A stem cell population (neoblasts) generates new cells and is comprised of pluripotent stem cells (cNeoblasts) and fate-specified cells (specialized neoblasts). Positional Information is constitutively active and harbored primarily in muscle, where it acts to guide stem cell-mediated tissue turnover and regeneration. I describe here a model in which Positional Information and stem cells combine to enable regeneration.
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two fgfrl wnt circuits organize the planarian anteroposterior axis
eLife, 2016Co-Authors: Lucila M Scimone, Lauren E. Cote, Travis Rogers, Peter W ReddienAbstract:How Positional Information instructs adult tissue maintenance is poorly understood. Planarians undergo whole-body regeneration and tissue turnover, providing a model for adult Positional Information studies. Genes encoding secreted and transmembrane components of multiple developmental pathways are predominantly expressed in planarian muscle cells. Several of these genes regulate regional identity, consistent with muscle harboring Positional Information. Here, single-cell RNA-sequencing of 115 muscle cells from distinct anterior-posterior regions identified 44 regionally expressed genes, including multiple Wnt and ndk/FGF receptor-like (ndl/FGFRL) genes. Two distinct FGFRL-Wnt circuits, involving juxtaposed anterior FGFRL and posterior Wnt expression domains, controlled planarian head and trunk patterning. ndl-3 and wntP-2 inhibition expanded the trunk, forming ectopic mouths and secondary pharynges, which independently extended and ingested food. fz5/8-4 inhibition, like that of ndk and wntA, caused posterior brain expansion and ectopic eye formation. Our results suggest that FGFRL-Wnt circuits operate within a body-wide coordinate system to control adult axial positioning.
David M Gardiner - One of the best experts on this subject based on the ideXlab platform.
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understanding Positional cues in salamander limb regeneration implications for optimizing cell based regenerative therapies
Disease Models & Mechanisms, 2014Co-Authors: Catherine D Mccusker, David M GardinerAbstract:Regenerative medicine has reached the point where we are performing clinical trials with stem-cell-derived cell populations in an effort to treat numerous human pathologies. However, many of these efforts have been challenged by the inability of the engrafted populations to properly integrate into the host environment to make a functional biological unit. It is apparent that we must understand the basic biology of tissue integration in order to apply these principles to the development of regenerative therapies in humans. Studying tissue integration in model organisms, where the process of integration between the newly regenerated tissues and the ‘old’ existing structures can be observed and manipulated, can provide valuable insights. Embryonic and adult cells have a memory of their original position, and this Positional Information can modify surrounding tissues and drive the formation of new structures. In this Review, we discuss the Positional interactions that control the ability of grafted cells to integrate into existing tissues during the process of salamander limb regeneration, and discuss how these insights could explain the integration defects observed in current cell-based regenerative therapies. Additionally, we describe potential molecular tools that can be used to manipulate the Positional Information in grafted cell populations, and to promote the communication of Positional cues in the host environment to facilitate the integration of engrafted cells. Lastly, we explain how studying Positional Information in current cell-based therapies and in regenerating limbs could provide key insights to improve the integration of cell-based regenerative therapies in the future.
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Positional Information is reprogrammed in blastema cells of the regenerating limb of the axolotl ambystoma mexicanum
PLOS ONE, 2013Co-Authors: Catherine D Mccusker, David M GardinerAbstract:The regenerating region of an amputated salamander limb, known as the blastema, has the amazing capacity to replace exactly the missing structures. By grafting cells from different stages and regions of blastemas induced to form on donor animals expressing Green Fluorescent Protein (GFP), to non-GFP host animals, we have determined that the cells from early stage blastemas, as well as cells at the tip of late stage blastemas are developmentally labile such that their Positional identity is reprogrammed by interactions with more proximal cells with stable Positional Information. In contrast, cells from the adjacent, more proximal stump tissues as well as the basal region of late bud blastemas are Positionally stable, and thus form ectopic limb structures when grafted. Finally, we have found that a nerve is required to maintain the blastema cells in a Positionally labile state, thus indicating a role for reprogramming cues in the blastema microenvironment.
Johannes Jaeger - One of the best experts on this subject based on the ideXlab platform.
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dynamic Positional Information patterning mechanism versus precision in gradient driven systems
Current Topics in Developmental Biology, 2020Co-Authors: Johannes Jaeger, Berta VerdAbstract:Abstract There is much talk about Information in biology. In developmental biology, this takes the form of “Positional Information,” especially in the context of morphogen-based pattern formation. Unfortunately, the concept of “Information” is rarely defined in any precise manner. Here, we provide two alternative interpretations of “Positional Information,” and examine the complementary meanings and uses of each concept. Positional Information defined as Shannon Information helps us understand decoding and error propagation in patterning systems. General relativistic Positional Information, in contrast, provides a metric to assess the output of pattern-forming mechanisms. Both interpretations provide powerful conceptual tools that do not compete, but are best used in combination to gain a proper mechanistic understanding of robust patterning.
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regulative feedback in pattern formation towards a general relativistic theory of Positional Information
Development, 2008Co-Authors: Johannes Jaeger, David Irons, Nicholas A M MonkAbstract:Positional specification by morphogen gradients is traditionally viewed as a two-step process. A gradient is formed and then interpreted, providing a spatial metric independent of the target tissue, similar to the concept of space in classical mechanics. However, the formation and interpretation of gradients are coupled, dynamic processes. We introduce a conceptual framework for Positional specification in which cellular activity feeds back on Positional Information encoded by gradients, analogous to the feedback between mass-energy distribution and the geometry of space-time in Einstein's general theory of relativity. We discuss how such general relativistic Positional Information (GRPI) can guide systems-level approaches to pattern formation.
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on the dynamic nature of Positional Information
BioEssays, 2006Co-Authors: Johannes Jaeger, John ReinitzAbstract:Morphogenetic fields are among the most fundamental concepts of embryology. However, they are also among the most ill-defined, since they consist of dynamic regulatory processes whose exact nature remains elusive. In order to achieve a more rigorous definition of a developmental field, Lewis Wolpert introduced the concept of Positional Information illustrated by his French Flag model. Here we argue that Wolpert's Positional Information—a static coordinate system defining a field—lacks essential properties of the original field concept. We show how data-driven mathematical modeling approaches now enable us to study regulatory processes in a way that is qualitatively different from our previous level of understanding. As an example, we review our recent analysis of segmentation gene expression in the blastoderm embryo of the fruit fly Drosophila melanogaster. Based on this analysis, we propose a revised French Flag, which incorporates the dynamic, feedback-driven nature of pattern formation in the Drosophila blastoderm. BioEssays 28: 1102–1111, 2006. © 2006 Wiley Periodicals, Inc.
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dynamic control of Positional Information in the early drosophila embryo
Nature, 2004Co-Authors: Johannes Jaeger, Hilde Janssens, Konstantin Kozlov, Svetlana Surkova, Maxim Blagov, David Kosman, Carlos E VanarioalonsoAbstract:Morphogen gradients contribute to pattern formation by determining Positional Information in morphogenetic fields. Interpretation of Positional Information is thought to rely on direct, concentration-threshold-dependent mechanisms for establishing multiple differential domains of target gene expression. In Drosophila, maternal gradients establish the initial position of boundaries for zygotic gap gene expression, which in turn convey Positional Information to pair-rule and segment-polarity genes, the latter forming a segmental pre-pattern by the onset of gastrulation. Here we report, on the basis of quantitative gene expression data, substantial anterior shifts in the position of gap domains after their initial establishment. Using a data-driven mathematical modelling approach, we show that these shifts are based on a regulatory mechanism that relies on asymmetric gap-gap cross-repression and does not require the diffusion of gap proteins. Our analysis implies that the threshold-dependent interpretation of maternal morphogen concentration is not sufficient to determine shifting gap domain boundary positions, and suggests that establishing and interpreting Positional Information are not independent processes in the Drosophila blastoderm.
Diego Echevarria - One of the best experts on this subject based on the ideXlab platform.
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Fgf8-related secondary organizers exert different polarizing planar instructions along the mouse anterior neural tube.
PloS one, 2012Co-Authors: Ivan Crespo-enriquez, Juha Partanen, Salvador Martinez, Diego EchevarriaAbstract:Early brain patterning depends on proper arrangement of Positional Information. This Information is given by gradients of secreted signaling molecules (morphogens) detected by individual cells within the responding tissue, leading to specific fate decisions. Here we report that the morphogen FGF8 exerts initially a differential signal activity along the E9.5 mouse neural tube. We demonstrate that this polarizing activity codes by RAS-regulated ERK1/2 signaling and depends on the topographical location of the secondary organizers: the isthmic organizer (IsO) and the anterior neural ridge (anr) but not on zona limitans intrathalamica (zli). Our results suggest that Sprouty2, a negative modulator of RAS/ERK pathway, is important for regulating Fgf8 morphogenetic signal activity by controlling Fgf8-induced signaling pathways and Positional Information during early brain development.
Catherine D Mccusker - One of the best experts on this subject based on the ideXlab platform.
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understanding Positional cues in salamander limb regeneration implications for optimizing cell based regenerative therapies
Disease Models & Mechanisms, 2014Co-Authors: Catherine D Mccusker, David M GardinerAbstract:Regenerative medicine has reached the point where we are performing clinical trials with stem-cell-derived cell populations in an effort to treat numerous human pathologies. However, many of these efforts have been challenged by the inability of the engrafted populations to properly integrate into the host environment to make a functional biological unit. It is apparent that we must understand the basic biology of tissue integration in order to apply these principles to the development of regenerative therapies in humans. Studying tissue integration in model organisms, where the process of integration between the newly regenerated tissues and the ‘old’ existing structures can be observed and manipulated, can provide valuable insights. Embryonic and adult cells have a memory of their original position, and this Positional Information can modify surrounding tissues and drive the formation of new structures. In this Review, we discuss the Positional interactions that control the ability of grafted cells to integrate into existing tissues during the process of salamander limb regeneration, and discuss how these insights could explain the integration defects observed in current cell-based regenerative therapies. Additionally, we describe potential molecular tools that can be used to manipulate the Positional Information in grafted cell populations, and to promote the communication of Positional cues in the host environment to facilitate the integration of engrafted cells. Lastly, we explain how studying Positional Information in current cell-based therapies and in regenerating limbs could provide key insights to improve the integration of cell-based regenerative therapies in the future.
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Positional Information is reprogrammed in blastema cells of the regenerating limb of the axolotl ambystoma mexicanum
PLOS ONE, 2013Co-Authors: Catherine D Mccusker, David M GardinerAbstract:The regenerating region of an amputated salamander limb, known as the blastema, has the amazing capacity to replace exactly the missing structures. By grafting cells from different stages and regions of blastemas induced to form on donor animals expressing Green Fluorescent Protein (GFP), to non-GFP host animals, we have determined that the cells from early stage blastemas, as well as cells at the tip of late stage blastemas are developmentally labile such that their Positional identity is reprogrammed by interactions with more proximal cells with stable Positional Information. In contrast, cells from the adjacent, more proximal stump tissues as well as the basal region of late bud blastemas are Positionally stable, and thus form ectopic limb structures when grafted. Finally, we have found that a nerve is required to maintain the blastema cells in a Positionally labile state, thus indicating a role for reprogramming cues in the blastema microenvironment.
