activin-2 is required for regeneration of polarity on the planarian anterior-posterior axis

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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Two FGFRL-Wnt circuits organize the planarian anteroposterior axis

eLife ◽

10.7554/elife.12845 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 54

Author(s):

M Lucila Scimone ◽

Lauren E Cote ◽

Travis Rogers ◽

Peter W Reddien

Keyword(s):

Regional Identity ◽

Muscle Cells ◽

Positional Information ◽

Whole Body ◽

Fgf Receptor ◽

Information Studies ◽

Genes Encoding ◽

Brain Expansion ◽

Control Adult ◽

Anterior Posterior

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.

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Nuclear receptor NR4A is required for patterning at the ends of the planarian anterior-posterior axis

eLife ◽

10.7554/elife.42015 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 1

Author(s):

Dayan J Li ◽

Conor L McMann ◽

Peter W Reddien

Keyword(s):

Gene Expression ◽

Nuclear Receptor ◽

Muscle Cells ◽

Positional Information ◽

Signaling Molecules ◽

Posterior Pole ◽

Positional Identity ◽

Tissue Turnover ◽

Anterior Posterior ◽

Abnormal Tissue

Positional information is fundamental to animal regeneration and tissue turnover. In planarians, muscle cells express signaling molecules to promote positional identity. At the ends of the anterior-posterior (AP) axis, positional identity is determined by anterior and posterior poles, which are putative organizers. We identified a gene, nr4A, that is required for anterior- and posterior-pole localization to axis extremes. nr4A encodes a nuclear receptor expressed predominantly in planarian muscle, including strongly at AP-axis ends and the poles. nr4A RNAi causes patterning gene expression domains to retract from head and tail tips, and ectopic anterior and posterior anatomy (e.g., eyes) to iteratively appear more internally. Our study reveals a novel patterning phenotype, in which pattern-organizing cells (poles) shift from their normal locations (axis extremes), triggering abnormal tissue pattern that fails to reach equilibrium. We propose that nr4A promotes pattern at planarian AP axis ends through restriction of patterning gene expression domains.

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DDX24, a D-E-A-D box RNA helicase, is required for muscle fiber organization and anterior pole specification essential for head regeneration in planarians

10.1101/2021.01.21.427618 ◽

2021 ◽

Author(s):

Souradeep R. Sarkar ◽

Vinay Kumar Dubey ◽

Anusha Jahagirdar ◽

Vairavan Lakshmanan ◽

Mohamed Mohamed Haroon ◽

...

Keyword(s):

Muscle Fiber ◽

Positional Information ◽

Rna Helicase ◽

Whole Body ◽

Rnai Phenotype ◽

Anterior Pole ◽

80S Ribosome ◽

Head Regeneration ◽

Fiber Organization

ABSTRACTPlanarians have a remarkable ability to undergo whole-body regeneration. The timely establishment of polarity at the wound site followed by the specification of the organizing centers- the anterior pole and the posterior pole, are indispensable for successful regeneration. In planarians, polarity, pole, and positional-information determinants are predominantly expressed by muscles. The molecular toolkit that enables this functionality of planarian muscles however remains poorly understood. Here we report that SMED_DDX24, a D-E-A-D Box RNA helicase and the homolog of human DDX24, is critical for planarian head regeneration. DDX24 is enriched in muscles and its knockdown leads to defective muscle-fiber organization and failure to re-specify anterior pole/organizer. Overall, loss of DDX24 manifests into gross misregulation of many well-characterized positional-control genes and patterning-control genes, necessary for organogenesis and tissue positioning and tissue patterning. In addition, wound-induced Wnt signalling was also upregulated in ddx24 RNAi animals. Canonical WNT-βCATENIN signalling is known to suppress head identity throughout bilateria, including planarians. Modulating this Wnt activity by β-catenin-1 RNAi, the effector molecule of this pathway, partially rescues the ddx24 RNAi phenotype, implying that a high Wnt environment in ddx24 knockdown animals likely impedes their normal head regeneration. Furthermore, at a sub-cellular level, RNA helicases are known to regulate muscle mass and function by regulating their translational landscape. ddx24 knockdown leads to the downregulation of large subunit ribosomal RNA and the 80S ribosome peak, implying its role in ribosome biogenesis and thereby influencing the translational output. This aspect seems to be an evolutionarily conserved role of DDX24. In summary, our work demonstrates the role of a D-E-A-D box RNA helicase in whole-body regeneration through muscle fiber organization, and pole and positional-information re-specification, likely mediated through translation regulation.

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Role of Perivascular Adipose Tissue-Derived Adiponectin in Vascular Homeostasis

Cells ◽

10.3390/cells10061485 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1485

Author(s):

Adrian Sowka ◽

Pawel Dobrzyn

Keyword(s):

Endothelial Cells ◽

Adipose Tissue ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells ◽

Vascular Wall ◽

Whole Body ◽

Perivascular Adipose Tissue

Studies of adipose tissue biology have demonstrated that adipose tissue should be considered as both passive, energy-storing tissue and an endocrine organ because of the secretion of adipose-specific factors, called adipokines. Adiponectin is a well-described homeostatic adipokine with metabolic properties. It regulates whole-body energy status through the induction of fatty acid oxidation and glucose uptake. Adiponectin also has anti-inflammatory and antidiabetic properties, making it an interesting subject of biomedical studies. Perivascular adipose tissue (PVAT) is a fat depot that is conterminous to the vascular wall and acts on it in a paracrine manner through adipokine secretion. PVAT-derived adiponectin can act on the vascular wall through endothelial cells and vascular smooth muscle cells. The present review describes adiponectin’s structure, receptors, and main signaling pathways. We further discuss recent studies of the extent and nature of crosstalk between PVAT-derived adiponectin and endothelial cells, vascular smooth muscle cells, and atherosclerotic plaques. Furthermore, we argue whether adiponectin and its receptors may be considered putative therapeutic targets.

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Analysis of sea star larval regeneration reveals conserved processes of whole-body regeneration across the metazoa

10.1101/118232 ◽

2017 ◽

Cited By ~ 2

Author(s):

Gregory Cary ◽

Andrew Wolff ◽

Olga ◽

Joseph Pattinato ◽

Veronica Hinman

Keyword(s):

Wound Response ◽

Tissue Type ◽

Whole Body ◽

Sea Star ◽

Proliferating Cells ◽

Evolutionary Origins ◽

Wide Range ◽

Gene Usage ◽

Patiria Miniata ◽

Anterior Posterior

ABSTRACTBackgroundMetazoan lineages exhibit a wide range of regenerative capabilities that vary among developmental stage and tissue type. The most robust regenerative abilities are apparent in the phyla Cnidaria, Platyhelminthes, and Echinodermata, whose members are capable of whole-body regeneration (WBR). This phenomenon has been well-characterized in planarian and hydra models, but the molecular details of WBR are less established within echinoderms, or any other deuterostome system. Thus, it is not clear to what degree aspects of this regenerative ability are due to deeply conserved mechanisms.ResultsWe characterize regeneration in the larval stage of the Bat Star (Patiria miniata). Following bisection along the anterior-posterior axis, larvae progress through phases of wound healing and re-proportioning of larval tissues. The overall number of proliferating cells is reduced following bisection and we find evidence for a re-deployment of genes with known roles in embryonic axial patterning. Following axial re-specification, we observe a significant localization of proliferating cells to the wound region. Analyses of transcriptome data highlight the molecular signatures of functions that are common to regeneration, including specific signaling pathways and cell cycle controls. Notably, we find evidence for temporal conservation among orthologous genes involved in regeneration from published Platyhelminth and Cnidarian regeneration datasets.ConclusionsThese analyses show that sea star larval regeneration includes phases of wound response, axis respecification, and wound proximal proliferation. Commonalities of the overall process of regeneration, as well as gene usage between this deuterostome and other species with divergent evolutionary origins suggest a deep conservation of whole-body regeneration among the metazoa.

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Whole-body imaging of neural and muscle activity during behavior in Hydra: bidirectional effects of osmolarity on contraction bursts

10.1101/2019.12.20.883835 ◽

2019 ◽

Author(s):

Wataru Yamamoto ◽

Rafael Yuste

Keyword(s):

Nervous System ◽

Body Size ◽

Neuronal Activity ◽

Environmental Conditions ◽

Muscle Activity ◽

Muscle Cells ◽

Major Effect ◽

Whole Body ◽

Effect Of Temperature ◽

Whole Body Imaging

AbstractThe neural code relates the activity of the nervous system to the activity of the muscles to the generation of behavior. To decipher it, it would be ideal to comprehensively measure the activity of the entire nervous system and musculature in a behaving animal. As a step in this direction, we used the cnidarian Hydra vulgaris to explore how physiological and environmental conditions alter the activity of the entire neural and muscle tissue and affect behavior. We used whole-body calcium imaging of neurons and muscle cells and studied the effect of temperature, media osmolarity, nutritional state and body size on body contractions.In mounted Hydra, changes in temperature, nutrition or body size did not have a major effect on neural or muscle activity, or on behavior. But changes in media osmolarity altered body contractions, increasing them in hipo-osmolar media solutions and decreasing them in hyperosmolar media. Similar effects were seen in ectodermal, but not in endodermal muscle. Osmolarity also bidirectionally changed the activity of contraction bursts neurons, but not of rhythmic potential neurons.These findings show osmolarity-dependent changes in neuronal activity, muscle activity, and contractions, consistent with the hypothesis that contraction burst neurons respond to media osmolarity, activating ectodermal muscle to generate contraction bursts. This dedicated circuit could serve as an excretory system to prevent osmotic injury. This work demonstrates the feasibility of studying the entire neuronal and muscle activity of behaving animals.Significance StatementWe imaged whole-body muscle and neuronal activity in Hydra in response to different physiological and environmental conditions. Osmolarity bidirectionally altered Hydra contractile behavior. These changes were accompanied by corresponding changes in the activity of one neuronal circuit and one set of muscles. This work is a step toward comprehensive deciphering of the mechanisms of animal behavior by measuring the activity of all neurons and muscle cells.

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Mutant expression of male copulatory bursa surface markers in Caenorhabditis elegans

Development ◽

10.1242/dev.103.3.485 ◽

1988 ◽

Vol 103 (3) ◽

pp. 485-495 ◽

Cited By ~ 1

Author(s):

C.D. Link ◽

C.W. Ehrenfels ◽

W.B. Wood

Keyword(s):

Positional Information ◽

Surface Expression ◽

Surface Markers ◽

Adult Males ◽

Vulval Development ◽

Altered Expression ◽

C Elegans ◽

Isolation And Characterization ◽

Cuticle Development ◽

Anterior Posterior

In a search for molecular markers of male tail morphogenesis in C. elegans, we have detected two surface markers that are specifically observed in the copulatory bursa of adult males and the vulva of adult hermaphrodites. These markers are defined by binding of a monoclonal antibody (Ab117) and the lectin wheat germ agglutinin (WGA) to live intact animals. Expression of these markers is dependent on sex, stage and anterior-posterior position in the animal. Four of ten mutants with specific defects in bursal development show altered expression of one or both markers. Because the WGA marker can be expressed in intersexual animals with very little bursal development, posterior surface expression of this marker can serve as an indication of subtle masculinization of hermaphrodites. The timing of expression of these markers is not affected by heterochronic mutations that cause larval animals to express adult cuticles or adult animals to express larval cuticles, indicating that marker expression can be uncoupled from general cuticle development. Mutant lin-22 males, which have an anterior-to-posterior transformation of cell fates in the lateral hypodermis, ectopically express both markers in a manner consistent with a ‘posteriorization’ of positional information in these animals. These markers should be useful for the isolation and characterization of mutants defective in bursal and vulval development, sex determination and expression of anterior-posterior positional information.

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Understanding Posturo-Occlusal Interrelationships by Combining Digital Occlusal and Posture Diagnostic Technologies

Advances in Medical Technologies and Clinical Practice - Handbook of Research on Clinical Applications of Computerized Occlusal Analysis in Dental Medicine ◽

10.4018/978-1-5225-9254-9.ch017 ◽

2020 ◽

pp. 1175-1242

Author(s):

Patrick Girouard, DMD MS

Keyword(s):

Contact Force ◽

Positional Information ◽

Body Posture ◽

Whole Body ◽

Dental Occlusion ◽

Occlusal Contact ◽

Research Software ◽

Stomatognathic System ◽

Combined Use ◽

Mapping Technology

The nature of the interrelationship between whole body posture and the quality of the dental occlusion has not yet to date been clearly documented within the dental or posture literature, as the findings of published studies within both fields have been scarce and inconclusive. The combined use of digital diagnostic occlusal and postural assessment technologies has not been widely employed in these research projects, which has mired both fields' ability to study, to understand, and to clearly ascertain how posture and dental occlusion affect each other physiologically. As such, the specific aims of this chapter are to outline how posture and dental occlusion interrelate through the stomatognathic system's afferent neural inputs into the central nervous system (CNS), which communicate important occlusal contact force distribution information, and equally as important, mandibular spatial positional information within the posture and balance regions of the brain. The concept that the dental occlusion is a capteur for posture (which in English means, a sensor of posture health), is further explored with the inclusion of three differing clinical posturo-occlusal cases, diagnosed and treated with the combined use of the T-Scan 9 computerized occlusal analysis technology, the MatScan/MobileMat foot pressure mapping technology, and the Footmat Research software version 7.10. These presented clinical cases illustrate that improved right-to-left occlusal contact force balance, and improved center of force location within the dental arches, improve a number of measurable sway parameters. Together, the implementation of the T-Scan and the MatScan exquisitely demonstrate to the clinician the significance of the physiologic interrelationship between body posture and the dental occlusion. The presented cases emphasize there exists a whole-body concept that depends upon a variety of differing systems, whereby changes in the dental occlusion produce a phenomenon of bio-functional neuro-reprogramming for the stomatognathic system and the whole body.

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Regulation of glucose transport and GLUT-1 expression by iron chelators in muscle cells in culture

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.269.6.e1052 ◽

1995 ◽

Vol 269 (6) ◽

pp. E1052-E1058 ◽

Cited By ~ 4

Author(s):

R. Potashnik ◽

N. Kozlovsky ◽

S. Ben-Ezra ◽

A. Rudich ◽

N. Bashan

Keyword(s):

Glucose Metabolism ◽

Glucose Uptake ◽

Glucose Transport ◽

Glucose Utilization ◽

Fold Increase ◽

Muscle Cells ◽

Iron Chelator ◽

Whole Body ◽

Iron Chelators ◽

Glut 1

Possible association between the degree of iron load and glucose metabolism has been postulated by both in vivo and in vitro studies. Because skeletal muscle plays a major role in whole body glucose utilization, we evaluated the effect of iron chelators deferoxamine (DFO) and bipyridyl (Bip) on glucose metabolism and transport in cultured L6 muscle cells. Bip (0.1 mM) or DFO (0.5 mM) added for 24 h to the culture medium increased glucose consumption, lactate production, and [14C]glucose incorporation into glycogen by approximately twofold. 2-Deoxy-glucose uptake by L6 myotubes increased time dependently, reaching a 5-fold and 2.5-fold increase after 12 h for Bip and DFO, respectively. Insulin induced a 2.5-fold increase in glucose uptake in untreated cells, which was additive to the chelator's effect. Iron chelator-induced glucose transport stimulation was inhibited by cycloheximide (2.5 micrograms/ml), indicating dependence on de novo protein synthesis. Increases in GLUT-1 protein and mRNA concentration, without changes in GLUT-4, were found to be responsible for iron chelator effects. We conclude that L6 cells adapt to reduction in iron availability by increasing glucose utilization through an enhanced expression of GLUT-1, without losing their physiological response to insulin.

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