1,721,011 research outputs found
Wnt Signaling and the Polarity of the Primary Body Axis
Full text linkHow animals establish and pattern the primary body axis is one of the most fundamental problems in biology. Data from diverse deuterostomes (frog, fish, mouse, and amphioxus) and from planarians (protostomes) suggest that Wnt signaling through β-catenin controls posterior identity during body plan formation in most bilaterally symmetric animals. Wnt signaling also influences primary axis polarity of pre-bilaterian animals, indicating that an axial patterning role for Wnt signaling predates the evolution of bilaterally symmetric animals. The use of posterior Wnt signaling and anterior Wnt inhibition might be a unifying principle of body plan development in most animals.National Institutes of Health (U.S.) (R01GM080639)American Cancer Society (RSG-07-180-01-DDC)Rita Allen FoundationSearle Scholars ProgramSmith FoundationW. M. Keck Foundatio
Polarized notum Activation at Wounds Inhibits Wnt Function to Promote Planarian Head Regeneration
No full textRegeneration requires initiation of programs tailored to the identity of missing parts. Head-versus-tail regeneration in planarians presents a paradigm for study of this phenomenon. After injury, Wnt signaling promotes tail regeneration. We report that wounding elicits expression of the Wnt inhibitor notum preferentially at anterior-facing wounds. This expression asymmetry occurs at essentially any wound, even if the anterior pole is intact. Inhibition of notum with RNA interference (RNAi) causes regeneration of an anterior-facing tail instead of a head, and double-RNAi experiments indicate that notum inhibits Wnt signaling to promote head regeneration. notum expression is itself controlled by Wnt signaling, suggesting that regulation of feedback inhibition controls the binary head-tail regeneration outcome. We conclude that local detection of wound orientation with respect to tissue axes results in distinct signaling environments that initiate appropriate regeneration responses.National Institutes of Health (U.S.) (R01GM080639)American Cancer Society (RSG-07-180-01-DDC
Constitutive gene expression and the specification of tissue identity in adult planarian biology
Full text linkPlanarians are flatworms that constitutively maintain adult tissues through cell turnover and can regenerate entire organisms from tiny body fragments. In addition to requiring new cells (from neoblasts), these feats require mechanisms that specify tissue identity in the adult. Crucial roles for Wnt and BMP signaling in the regeneration and maintenance of the body axes have been uncovered, among other regulatory factors. Available data indicate that genes involved in positional identity regulation at key embryonic stages in other animals display persisting regionalized expression in adult planarians. These expression patterns suggest that a constitutively active gene expression map exists for the maintenance of the planarian body. Planarians thus present a fertile ground for the identification of factors regulating the regionalization of the metazoan body plan and for the study of the attributes of these factors that can lead to the maintenance and regeneration of adult tissues.National Institutes of Health (U.S.) (R01GM080639)American Cancer Society (RSG-07-180-01-DDC)W. M. Keck Foundatio
Planarian regeneration involves distinct stem cell responses to wounds and tissue absence
Full text linkRegeneration requires signaling from a wound site for detection of the wound and a mechanism that determines the nature of the injury to specify the appropriate regenerative response. Wound signals and tissue responses to wounds that elicit regeneration remain poorly understood. Planarians are able to regenerate from essentially any type of injury and present a novel system for the study of wound responses in regeneration initiation. Newly developed molecular and cellular tools now enable study of regeneration initiation using the planarian Schmidtea mediterranea. Planarian regeneration requires adult stem cells called neoblasts and amputation triggers two peaks in neoblast mitoses early in regeneration. We demonstrate that the first mitotic peak is a body-wide response to any injury and that a second, local, neoblast response is induced only when injury results in missing tissue. This second response was characterized by recruitment of neoblasts to wounds, even in areas that lack neoblasts in the intact animal. Subsequently, these neoblasts were induced to divide and differentiate near the wound, leading to formation of new tissue. We conclude that there exist two functionally distinct signaling phases of the stem cell wound response that distinguish between simple injury and situations that require the regeneration of missing tissue.National Institutes of Health (U.S.) (R01GM080639)American Cancer Society (RSG-07-180-01-DDC)W. M. Keck FoundationThomas D. and Virginia W. Cabot (Career Development Professorship)Searle Scholars ProgramSmith FoundationRita Allen Foundatio
The Cellular Basis for Animal Regeneration
No full textThe ability of animals to regenerate missing parts is a dramatic and poorly understood aspect of biology. The sources of new cells for these regenerative phenomena have been sought for decades. Recent advances involving cell fate tracking in complex tissues have shed new light on the cellular underpinnings of regeneration in Hydra, planarians, zebrafish, Xenopus, and Axolotl. Planarians accomplish regeneration with use of adult pluripotent stem cells, whereas several vertebrates utilize a collection of lineage-restricted progenitors from different tissues. Together, an array of cellular strategies—from pluripotent stem cells to tissue-specific stem cells and dedifferentiation—are utilized for regeneration
Transcriptome Analysis of the Planarian Eye Identifies ovo as a Specific Regulator of Eye Regeneration
No full textAmong the millions of invertebrate species with visual systems, the genetic basis of eye development and function is well understood only in Drosophila melanogaster. We describe an eye transcriptome for the planarian Schmidtea mediterranea. Planarian photoreceptors expressed orthologs of genes required for phototransduction and microvillus structure in Drosophila and vertebrates, and optic pigment cells expressed solute transporters and melanin synthesis enzymes similar to those active in the vertebrate retinal pigment epithelium. Orthologs of several planarian eye genes, such as bestrophin-1 and Usher syndrome genes, cause eye defects in mammals when perturbed and were not previously described to have roles in invertebrate eyes. Five previously undescribed planarian eye transcription factors were required for normal eye formation during head regeneration. In particular, a conserved, transcription-factor-encoding ovo gene was expressed from the earliest stages of eye regeneration and was required for regeneration of all cell types of the eye.National Institutes of Health (U.S.) (NIH (R01GM08063)W. M. Keck Foundatio
A Bmp/Admp Regulatory Circuit Controls Maintenance and Regeneration of Dorsal-Ventral Polarity in Planarians
No full textAnimal embryos have diverse anatomy and vary greatly in size. It is therefore remarkable that a common signaling pathway, BMP signaling, controls development of the dorsoventral (DV) axis throughout the Bilateria [1, 2, 3, 4, 5, 6, 7 and 8]. In vertebrates, spatially opposed expression of the BMP family proteins Bmp4 and Admp (antidorsalizing morphogenetic protein) can promote restoration of DV pattern following tissue removal [9, 10 and 11]. bmp4 orthologs have been identified in all three groups of the Bilateria (deuterostomes, ecdysozoans, and lophotrochozoans) [12]. By contrast, the absence of admp orthologs in ecdysozoans such as Drosophila and C. elegans has suggested that a regulatory circuit of oppositely expressed bmp4 and admp genes represents a deuterostome-specific innovation. Here we describe the existence of spatially opposed bmp and admp expression in a protostome. An admp ortholog (Smed-admp) is expressed ventrally and laterally in adult Schmidtea mediterranea planarians, opposing the dorsal-pole expression of Smed-bmp4. Smed-admp is required for regeneration following parasagittal amputation. Furthermore, Smed-admp promotes Smed-bmp4 expression and Smed-bmp4 inhibits Smed-admp expression, generating a regulatory circuit that buffers against perturbations of Bmp signaling. These results suggest that a Bmp/Admp regulatory circuit is a central feature of the Bilateria, used broadly for the establishment, maintenance, and regeneration of the DV axis.National Institutes of Health (U.S.) (R01GM080639)American Cancer Society (RSG-07-180-01-DDC)W. M. Keck FoundationThomas D. and Virginia W. Cabot (Career Development Professorship
dlx and sp6-9 Control Optic Cup Regeneration in a Prototypic Eye
No full textOptic cups are a structural feature of diverse eyes, from simple pit eyes to camera eyes of vertebrates and cephalopods. We used the planarian prototypic eye as a model to study the genetic control of optic cup formation and regeneration. We identified two genes encoding transcription factors, sp6-9 and dlx, that were expressed in the eye specifically in the optic cup and not the photoreceptor neurons. RNAi of these genes prevented formation of visible optic cups during regeneration. Planarian regeneration requires an adult proliferative cell population with stem cell-like properties called the neoblasts. We found that optic cup formation occurred only after migration of progressively differentiating progenitor cells from the neoblast population. The eye regeneration defect caused by dlx and sp6-9 RNAi can be explained by a failure to generate these early optic cup progenitors. Dlx and Sp6-9 genes function as a module during the development of diverse animal appendages, including vertebrate and insect limbs. Our work reveals a novel function for this gene pair in the development of a fundamental eye component, and it utilizes these genes to demonstrate a mechanism for total organ regeneration in which extensive cell movement separates new cell specification from organ morphogenesis.United States. National Institutes of Health (NIH R01GM080639)W. M. Keck FoundationHoward Hughes Medical Institut
A Generic and Cell-Type-Specific Wound Response Precedes Regeneration in Planarians
Full text linkSummaryRegeneration starts with injury. Yet how injuries affect gene expression in different cell types and how distinct injuries differ in gene expression remain unclear. We defined the transcriptomes of major cell types of planarians—flatworms that regenerate from nearly any injury—and identified 1,214 tissue-specific markers across 13 cell types. RNA sequencing on 619 single cells revealed that wound-induced genes were expressed either in nearly all cell types or specifically in one of three cell types (stem cells, muscle, or epidermis). Time course experiments following different injuries indicated that a generic wound response is activated with any injury regardless of the regenerative outcome. Only one gene, notum, was differentially expressed early between anterior- and posterior-facing wounds. Injury-specific transcriptional responses emerged 30 hr after injury, involving context-dependent patterning and stem-cell-specialization genes. The regenerative requirement of every injury is different; however, our work demonstrates that all injuries start with a common transcriptional response
Acoel regeneration mechanisms indicate an ancient role for muscle in regenerative patterning
Full text linkPositional information is required for animal regeneration, yet how it is harbored in adult tissues is poorly understood. In planarians, positional control genes (PCGs) control regeneration outcomes and are regionally expressed predominately in the musculature. Acoels are early diverging bilaterally symmetric animals, having separated from other bilaterians > 550 million years ago. Here, we find that PCGs in the acoel Hofstenia miamia are expressed together and specifically in a primary differentiated cell type: muscle. The vast majority of Hofstenia muscle cells in regions tested express PCGs, suggesting positional information is a major feature of muscle. PCG expression domains are dynamic in muscle after injury, consistent with known PCG roles in guiding regeneration. These data demonstrate an instructive positional role for Hofstenia muscle and this similarity with planarians suggests mesodermal muscle originated at the base of the Bilateria not only for contraction, but also as the source of positional information guiding regeneration.Version of Recor
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