The Experts below are selected from a list of 53796 Experts worldwide ranked by ideXlab platform
Shalika Kumburegama - One of the best experts on this subject based on the ideXlab platform.
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Strabismus-mediated primary archenteron invagination is uncoupled from Wnt/β-catenin-dependent endoderm cell fate specification in Nematostella vectensis (Anthozoa, Cnidaria): Implications for the evolution of gastrulation.
Evodevo, 2011Co-Authors: Shalika Kumburegama, Naveen M. Wijesena, Ronghui Xu, Athula H. WikramanayakeAbstract:Background Gastrulation is a uniquely metazoan character, and its genesis was arguably the key step that enabled the remarkable diversification within this clade. The process of gastrulation involves two tightly coupled events during embryogenesis of most metazoans. Morphogenesis produces a distinct internal epithelial layer in the embryo, and this epithelium becomes segregated as an endoderm/endomesodermal germ layer through the activation of a specific gene Regulatory Program. The developmental mechanisms that induced archenteron formation and led to the segregation of germ layers during metazoan evolution are unknown. But an increased understanding of development in early diverging taxa at the base of the metazoan tree may provide insights into the origins of these developmental mechanisms.
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strabismus mediated primary archenteron invagination is uncoupled from wnt β catenin dependent endoderm cell fate specification in nematostella vectensis anthozoa cnidaria implications for the evolution of gastrulation
Evodevo, 2011Co-Authors: Shalika Kumburegama, Naveen M. Wijesena, Ronghui Xu, Athula H. WikramanayakeAbstract:Background Gastrulation is a uniquely metazoan character, and its genesis was arguably the key step that enabled the remarkable diversification within this clade. The process of gastrulation involves two tightly coupled events during embryogenesis of most metazoans. Morphogenesis produces a distinct internal epithelial layer in the embryo, and this epithelium becomes segregated as an endoderm/endomesodermal germ layer through the activation of a specific gene Regulatory Program. The developmental mechanisms that induced archenteron formation and led to the segregation of germ layers during metazoan evolution are unknown. But an increased understanding of development in early diverging taxa at the base of the metazoan tree may provide insights into the origins of these developmental mechanisms.
Kristy A.n Bulleit - One of the best experts on this subject based on the ideXlab platform.
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Achieving sustainable development: a review of the environmental balancing act in two key clean water act Regulatory Programs
Environmental Science & Policy, 2000Co-Authors: Kristy A.n BulleitAbstract:The goal of achieving "sustainable development" has been embraced by a wide range of stakeholders interested in protecting both the environment and the economy in the United States and globally. The Clean Water Act ("CWA" or the "Act") includes important Regulatory provisions that contemplate the application of sustainable development principles. Yet implementing those Programs often raises substantial debate about what sustainable development means, what course of action it requires, and the availability and adequacy of tools to measure or predict whether a given level of use or development is sustainable. Failure to confront those questions can lead to imprudent or wasteful decisions. This paper first will briefly describe the ongoing evolution of sustainable development concepts in the United States, with particular focus on the recommendations of the President's Council on Sustainable Development. Then, it will examine the applicability of those concepts to two important Clean Water Act Regulatory Programs -- the S316(b) Regulatory Program for cooling water intake structures and the state water quality standards Program -- both of which are now under evaluation.
Elisabeth Paietta - One of the best experts on this subject based on the ideXlab platform.
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musashi2 sustains the mixed lineage leukemia driven stem cell Regulatory Program
Journal of Clinical Investigation, 2015Co-Authors: Sun Mi Park, Mithat Gonen, Gerard Minuesa, Patrick Tivnan, Trevor S Barlowe, James Taggart, Raquel P Deering, Nir Hacohen, Maria E Figueroa, Elisabeth PaiettaAbstract:Leukemia stem cells (LSCs) are found in most aggressive myeloid diseases and contribute to therapeutic resistance. Leukemia cells exhibit a dysregulated developmental Program as the result of genetic and epigenetic alterations. Overexpression of the RNA-binding protein Musashi2 (MSI2) has been previously shown to predict poor survival in leukemia. Here, we demonstrated that conditional deletion of Msi2 in the hematopoietic compartment results in delayed leukemogenesis, reduced disease burden, and a loss of LSC function in a murine leukemia model. Gene expression profiling of these Msi2-deficient animals revealed a loss of the hematopoietic/leukemic stem cell self-renewal Program and an increase in the differentiation Program. In acute myeloid leukemia patients, the presence of a gene signature that was similar to that observed in Msi2-deficent murine LSCs correlated with improved survival. We determined that MSI2 directly maintains the mixed-lineage leukemia (MLL) self-renewal Program by interacting with and retaining efficient translation of Hoxa9, Myc, and Ikzf2 mRNAs. Moreover, depletion of MLL target Ikzf2 in LSCs reduced colony formation, decreased proliferation, and increased apoptosis. Our data provide evidence that MSI2 controls efficient translation of the oncogenic LSC self-renewal Program and suggest MSI2 as a potential therapeutic target for myeloid leukemia.
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msi2 maintains the mll leukemia stem cell Regulatory Program
Blood, 2014Co-Authors: Sun Mi Park, Mithat Gonen, Gerard Minuesa, Patrick Tivnan, Trevor S Barlowe, James Taggart, Raquel P Deering, Nir Hacohen, Maria E Figueroa, Elisabeth PaiettaAbstract:Leukemia stem cells (LSCs) are found in most aggressive myeloid diseases and contribute to therapeutic resistance. LSCs are characterized by their gain of a self-renewal Program that is normally associated with hematopoietic stem cells (HSCs). Previously we have shown that the RNA binding protein, Msi2 contributes to both HSC and myeloid leukemia function. Elevated MSI2 expression predicts a poor prognosis in a variety of leukemias and shRNA-mediated depletion in human AML cell lines reduces proliferation, increases differentiation and induces apoptosis. Despite these in vitro and correlative studies, MSI2’s molecular mechanism is not known and its role in LSC function has not been assessed. To elucidate MSI2’s role in LSC function, we utilized the MLL-AF9 leukemia mouse model. Initially we found MSI2 was elevated in the LSC enriched compartment (c-KitHigh cells) compared to non-LSCs (c-KitLow cells) based on flow cytometric intracellular staining. Therefore, to establish a model to study Msi2 and its contribution to myeloid LSCs, we have utilized the Msi2 conditional knockout mice that we previously crossed ( Msi2f/f ) into an Mx1-Cre background to generate the Msi2 Δ / Δ allele (injection of polyinositol-polycytosine; pIpC). In order to test if Msi2 is critical for MLL-AF9 mediated initiation, we transduced control Msi2f/f and Msi2 Δ / Δ Lin- Sca1+ c-Kit+cells (LSKs) with MLL-AF9 expressing retroviruses co-expressing GFP. Msi2 deleted LSKs or granulocyte-monocyte progenitors (GMPs) transduced with MLL-AF9 demonstrated delayed leukemogenesis with dramatically reduced diseased burden. Msi2 deficient leukemias were found to have a 4-fold reduced phenotypic LSC population and were more differentiated based on cellular morphology. Msi2 deficient leukemias failed to transplant into secondary recipients demonstrating that Msi2 is required for maintaining LSCs. Deletion of Msi2 after leukemia engraftment led to a delay in leukemogenesis indicating that Msi2 is also important for leukemia maintenance. Gene expression profiling of the Msi2 ablated LSCs resulted in a loss of the HSC/LSC Program and an increase in differentiation gene sets. The gene signature from the Msi2 deleted murine LSCs (121 genes) was overlapped and subjected to unsupervised clustering with the gene expression profiles from 336 AML patients (ECOG1900 dataset). This analysis resulted in distinct clusters that had differential MSI2 expression and the MSI2 “high” cluster predicted a worse clinical outcome when compared to the other clusters. Overlapping of the differential transcriptional analysis of the Msi2 deleted murine LSCs with our global MSI2 direct mRNA targets (HITS-CLIP) led us to identify that MSI2 binds to transcripts that are associated with the downstream MLL self-renewal Program, including Myc and Ikzf2 . Ikzf2 is a member of the Ikaros transcription factor family and is known to regulate lymphocyte development by controlling Regulatory T-cell function and chromatin remodeling. Ikzf2 shRNA mediated depletion resulted in reduced colony formation, decreased proliferation and increased apoptosis. The MLL associated targets were also reduced, which included Bcl-2 and Hoxa9 . In contrast to its tumor suppressor role in hypodiploid B-ALL, these results suggest that Ikzf2 contributes to MLL leukemia cell maintenance. Thus, we provide evidence that MSI2 maintains the oncogenic LSC epigenetic Program and the rationale for clinically targeting MSI2 in myeloid leukemia. Disclosures No relevant conflicts of interest to declare.
Athula H. Wikramanayake - One of the best experts on this subject based on the ideXlab platform.
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Strabismus-mediated primary archenteron invagination is uncoupled from Wnt/β-catenin-dependent endoderm cell fate specification in Nematostella vectensis (Anthozoa, Cnidaria): Implications for the evolution of gastrulation.
Evodevo, 2011Co-Authors: Shalika Kumburegama, Naveen M. Wijesena, Ronghui Xu, Athula H. WikramanayakeAbstract:Background Gastrulation is a uniquely metazoan character, and its genesis was arguably the key step that enabled the remarkable diversification within this clade. The process of gastrulation involves two tightly coupled events during embryogenesis of most metazoans. Morphogenesis produces a distinct internal epithelial layer in the embryo, and this epithelium becomes segregated as an endoderm/endomesodermal germ layer through the activation of a specific gene Regulatory Program. The developmental mechanisms that induced archenteron formation and led to the segregation of germ layers during metazoan evolution are unknown. But an increased understanding of development in early diverging taxa at the base of the metazoan tree may provide insights into the origins of these developmental mechanisms.
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strabismus mediated primary archenteron invagination is uncoupled from wnt β catenin dependent endoderm cell fate specification in nematostella vectensis anthozoa cnidaria implications for the evolution of gastrulation
Evodevo, 2011Co-Authors: Shalika Kumburegama, Naveen M. Wijesena, Ronghui Xu, Athula H. WikramanayakeAbstract:Background Gastrulation is a uniquely metazoan character, and its genesis was arguably the key step that enabled the remarkable diversification within this clade. The process of gastrulation involves two tightly coupled events during embryogenesis of most metazoans. Morphogenesis produces a distinct internal epithelial layer in the embryo, and this epithelium becomes segregated as an endoderm/endomesodermal germ layer through the activation of a specific gene Regulatory Program. The developmental mechanisms that induced archenteron formation and led to the segregation of germ layers during metazoan evolution are unknown. But an increased understanding of development in early diverging taxa at the base of the metazoan tree may provide insights into the origins of these developmental mechanisms.
Mansi Srivastava - One of the best experts on this subject based on the ideXlab platform.
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a Regulatory Program for initiation of wnt signaling during posterior regeneration
Cell Reports, 2020Co-Authors: Alyson N Ramirez, Kaitlyn Loubetsenear, Mansi SrivastavaAbstract:Whole-body regeneration relies on the re-establishment of body axes for patterning of new tissue. Wnt signaling is required to correctly regenerate tissues along the primary axis in many animals. However, the causal mechanisms that first launch Wnt signaling during regeneration are poorly characterized. We use the acoel worm Hofstenia miamia to identify processes that initiate Wnt signaling during posterior regeneration and find that the ligand wnt-3 is upregulated early in posterior-facing wounds. Functional studies reveal that wnt-3 is required to regenerate posterior tissues. wnt-3 is expressed in stem cells, it is needed for their proliferation, and its function is stem cell dependent. Chromatin accessibility data reveal that wnt-3 activation requires input from the general wound response. In addition, the expression of a different Wnt ligand, wnt-1, before amputation is required for wound-induced activation of wnt-3. Our study establishes a gene Regulatory network for initiating Wnt signaling in posterior tissues in a bilaterian.
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a Regulatory Program for initiation of wnt signaling during posterior regeneration
bioRxiv, 2020Co-Authors: Alyson N Ramirez, Kaitlyn Loubetsenear, Mansi SrivastavaAbstract:Summary Whole-body regeneration requires the re-establishment of body axes for appropriate patterning of new and old tissue. Wnt signaling has been utilized to correctly regenerate tissues along the primary axis in many animals. However, the causal molecular mechanisms that first launch Wnt signaling during regeneration are poorly characterized. We used the acoel worm Hofstenia miamia to identify processes that initiate Wnt signaling. Transcriptome profiling, in situ hybridization, and functional studies revealed a Wnt ligand, wnt-3, as an early wound-induced gene specifically activated in posterior-facing wound sites and was required for establishing posterior identity during regeneration. wnt-3 was upregulated upon amputation in stem cells, and its inhibition affected stem cell proliferation. Ectopic expression of anterior markers in wnt-3 RNAi head fragments was stem cell dependent. Chromatin accessibility data revealed that wnt-3 activation during regeneration required input from the general wound response. Additionally, the expression of a different Wnt ligand, wnt-1, prior to amputation was required for activation of wound-induced wnt-3 expression. Our study establishes a gene Regulatory network for initiating Wnt signaling in posterior tissues in a bilaterian.
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a Regulatory Program for excretory system regeneration in planarians
Development, 2011Co-Authors: Lucila M Scimone, Mansi Srivastava, George W Bell, Peter W ReddienAbstract:Planarians can regenerate any missing body part, requiring mechanisms for the production of organ systems in the adult, including their prominent tubule-based filtration excretory system called protonephridia. Here, we identify a set of genes, Six1/2-2, POU2/3, hunchback, Eya and Sall, that encode transcription Regulatory proteins that are required for planarian protonephridia regeneration. During regeneration, planarian stem cells are induced to form a cell population in regeneration blastemas expressing Six1/2-2, POU2/3, Eya, Sall and Osr that is required for excretory system formation. POU2/3 and Six1/2-2 are essential for these precursor cells to form. Eya, Six1/2-2, Sall, Osr and POU2/3-related genes are required for vertebrate kidney development. We determined that planarian and vertebrate excretory cells express homologous proteins involved in reabsorption and waste modification. Furthermore, we identified novel nephridia genes. Our results identify a transcriptional Program and cellular mechanisms for the regeneration of an excretory organ and suggest that metazoan excretory systems are regulated by genetic Programs that share a common evolutionary origin.