Papers by Jeanne Wilson-Rawls
Activation of musculoskeletal development and repair mechanisms in the regenerating lizard tail (344.7)
The FASEB Journal
Uniquely among amniote vertebrates, lizards can lose their tails and regrow a functional replacem... more Uniquely among amniote vertebrates, lizards can lose their tails and regrow a functional replacement. These regenerated tails, which have an organization distinct from the original tail, contain newly formed hyaline cartilage, muscle, vasculature, spinal cord, and skin. Using Illumina RNA‐Seq technology, we have identified over 300 differentially expressed (DE) genes along the proximal/distal axis of the regenerating tail at a mid‐growth stage (n=5). Histological and immunohistological analysis reflect these transcriptomic data. Specifically, there are proliferative cells throughout the proximal/distal axis and proliferative markers are expressed throughout the proximal/distal axis. However, cells progressively show differentiation towards the proximal region of the regenerating tail, and genes with high expression in this region include myogenic regulators and factors for muscle structure and differentiation. In contrast, genes with high expression in the regenerating tail tip incl...
Anole Lizard Genomes: A Window into Amniote Regeneration and Understanding the Genetic Etiology of Human Musculoskeletal Disorders
ABSTRACT Uniquely among amniote vertebrates, lizards can lose their tails and regrow a functional... more ABSTRACT Uniquely among amniote vertebrates, lizards can lose their tails and regrow a functional replacement. These regenerated tails contain newly formed hyaline cartilage, spinal cord, skeletal muscle, and skin. Progress in studying the cellular and molecular mechanisms of lizard regeneration has been limited by lack of genomic resources. With the release of the genome of the green anole, Anolis carolinensis, and our deep transcriptome based annotation of this genome (Eckalbar et al., 2013), we have a unique opportunity to identify the cells and pathways activated in lizard regeneration. We have quantified the transcriptomic profile along the proximal to distal axis of the regenerating tail, compared to adult tissues and stem cell rich tissues. Gene Ontology groups with elevated expression at the growing tail tip include members of key developmental regulatory pathways, including the MAPK signaling and Wnt/beta-catenin pathways, response to wounding and inflammation, thyroid hormone generation, and skeletal system development. GO groups elevated in the proximal differentiating tail include muscle contraction, regulation of ATPase activity, and biological adhesion. These studies have identified components of a genetic program for regeneration in the lizard that includes both developmental and adult repair mechanisms, applicable for future regenerative medical therapies. Anole lizards are also a spectacular example of adaptive radiation in vertebrates, with musculoskeletal adaptations for specific ecological niches. In order to identify the coding and cis-regulatory changes that drive these adaptations, we have completed whole genome sequencing of three neotropical anole species: the grass anole (A. auratus), the Central American giant anole (A. frenatus), and the slender anole (A. apletophallus). Functional anatomical and histological studies are being performed to quantify the tail and hindlimb muscle groups of these species compared to A. carolinensis. We expect that these anatomical data combined with comparative analysis of coding and regulatory sequences will allow us to identify the divergent alleles associated with changes in anole musculoskeletal development. These studies will help to identify conserved amniote regulatory networks and enhancer sequences that are relevant to understanding the etiology of human musculoskeletal disorders. Acknowledgements: NIH grants NCRR/ORIP R21RR031305 and NIAMS R21AR064935, grant 1113 from the Arizona Biomedical Research Commission, and funding from Arizona State University and the Smithsonian Tropical Research Institute.
P210 Bcr-Abl interacts with the interleukin 3 receptor beta(c) subunit and constitutively induces its tyrosine phosphorylation
PubMed, Aug 1, 1996
Chronic myelogenous leukemia is a neoplasm of pluripotent hematopoietic cells. The P210 Bcr-Abl o... more Chronic myelogenous leukemia is a neoplasm of pluripotent hematopoietic cells. The P210 Bcr-Abl oncoprotein is a deregulated cytoplasmic tyrosine kinase that has been shown to cause chronic myelogenous leukemia-like neoplasms in mice. Cytokines such as interleukin 3 and granulocyte/macrophage-colony-stimulating factor regulate the growth and differentiation of hematopoietic precursors. These cytokines activate two distinct signals to the nucleus. One signal is through the Ras pathway, and the second involves activation of Jak2. We demonstrated that Bcr-Abl co-immunoprecipitates with, and constitutively phosphorylates, the common beta(c) subunit of the interleukin 3 and granulocyte/macrophage-colony-stimulating factor receptors. Our data show that formation of this complex leads to the constitutive tyrosine phosphorylation of Jak2. It has been demonstrated that Bcr-Abl interacts with Grb2 and Shc, which in turn activates the Ras pathway. Our new findings raise the possibility that Bcr-Abl activates signaling through both pathways in a factor-independent fashion.
P210 Bcr-Abl interacts with the interleukin-3 beta c subunit and constitutively activates Jak2
PubMed, Apr 1, 1997
Chronic myelogenous leukemia is a neoplasm of pluripotent hematopoietic cells. Cytokines such as ... more Chronic myelogenous leukemia is a neoplasm of pluripotent hematopoietic cells. Cytokines such as interleukin-3 and granulocyte-macrophage colony-stimulating factor regulate the growth and differentiation of hematopoietic precursors. These cytokines activate two distinct signals to the nucleus. One signal is through the Ras pathway, and the second involves activation of Jak2. We demonstrated that Bcr-Abl co-immunoprecipitates with and constitutively phosphorylates the common beta c chain of the interleukin-3 (IL-3) and granulocyte-macrophage-macrophage colony-stimulating factor (GM-CSF) receptors. Our data show that formation of this complex leads to the constitutive activation of Jak2. Previously, it has been demonstrated that Bcr-Abl interacts with Grb2 and Shc, which in turn activates the Ras pathway. Thus, Bcr-Abl can activate signalling through both pathways in a factor-independent fashion.
Biomolecules
Muscular dystrophies are a heterogeneous group of genetic muscle-wasting disorders that are subdi... more Muscular dystrophies are a heterogeneous group of genetic muscle-wasting disorders that are subdivided based on the region of the body impacted by muscle weakness as well as the functional activity of the underlying genetic mutations. A common feature of the pathophysiology of muscular dystrophies is chronic inflammation associated with the replacement of muscle mass with fibrotic scarring. With the progression of these disorders, many patients suffer cardiomyopathies with fibrosis of the cardiac tissue. Anti-inflammatory glucocorticoids represent the standard of care for Duchenne muscular dystrophy, the most common muscular dystrophy worldwide; however, long-term exposure to glucocorticoids results in highly adverse side effects, limiting their use. Thus, it is important to develop new pharmacotherapeutic approaches to limit inflammation and fibrosis to reduce muscle damage and promote repair. Here, we examine the pathophysiology, genetic background, and emerging therapeutic strate...
Frontiers in Cell and Developmental Biology, 2023
Background: The expression of proinflammatory signals at the site of muscle injury are essential ... more Background: The expression of proinflammatory signals at the site of muscle injury are essential for efficient tissue repair and their dysregulation can lead to inflammatory myopathies. Macrophages, neutrophils, and fibroadipogenic progenitor cells residing in the muscle are significant sources of proinflammatory cytokines and chemokines. However, the inducibility of the myogenic satellite cell population and their contribution to proinflammatory signaling is less understood. Methods: Mouse satellite cells were isolated and exposed to lipopolysaccharide (LPS) to mimic sterile skeletal muscle injury and changes in the expression of proinflammatory genes was examined by RT-qPCR and single cell RNA sequencing. Expression patterns were validated in skeletal muscle injured with cardiotoxin by RT-qPCR and immunofluorescence. Results: Satellite cells in culture were able to express Tnfa, Ccl2, and Il6, within 2 h of treatment with LPS. Single cell RNA-Seq revealed seven cell clusters representing the continuum from activation to differentiation. LPS treatment led to a heterogeneous pattern of induction of CC and C-X-C chemokines (e.g., Ccl2, Ccl5, and Cxcl0) and cytokines (e.g., Tgfb1, Bmp2, Il18, and Il33) associated with innate immune cell recruitment and satellite cell proliferation. One cell cluster was enriched for expression of the antiviral interferon pathway genes under control conditions and LPS treatment. Activation of this pathway in satellite cells was also detectable at the site of cardiotoxin induced muscle injury. Conclusion: These data demonstrate that satellite cells respond to inflammatory signals and secrete chemokines and cytokines. Further, we identified a previously unrecognized subset of satellite cells that may act as sensors for muscle infection or injury using the antiviral interferon pathway.
Comparison of myoblast and satellite cell behavior on scaffolds: Analysis of proliferation and differentiation
Orthopedic & muscular system, May 17, 2016
Comparison of myoblast and satellite cell behavior on scaffolds: Analysis of proliferation and differentiation
Orthopedic & muscular system, May 17, 2016
Biomedicines
Duchenne muscular dystrophy is an X-linked disease afflicting 1 in 3500 males that is characteriz... more Duchenne muscular dystrophy is an X-linked disease afflicting 1 in 3500 males that is characterized by muscle weakness and wasting during early childhood, and loss of ambulation and death by early adulthood. Chronic inflammation due to myofiber instability leads to fibrosis, which is a primary cause of loss of ambulation and cardiorespiratory insufficiency. Current standard of care focuses on reducing inflammation with corticosteroids, which have serious adverse effects. It is imperative to identify alternate immunosuppressants as treatments to reduce fibrosis and mortality. Serp-1, a Myxoma virus-derived 55 kDa secreted glycoprotein, has proven efficacy in a range of animal models of acute inflammation, and its safety and efficacy has been shown in a clinical trial. In this initial study, we examined whether pegylated Serp-1 (PEGSerp-1) treatment would ameliorate chronic inflammation in a mouse model for Duchenne muscular dystrophy. Our data revealed a significant reduction in diap...
Stem Cell Biology and Regenerative Medicine, 2016
the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustra... more the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.
Stem Cell Biology and Regenerative Medicine, 2016
the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustra... more the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.
Single cell analysis reveals satellite cell heterogeneity for proinflammatory chemokine expression
Frontiers in Cell and Developmental Biology, 2023
Isolation of Anolis carolinensis satellite cells and examination of their differentiation potential
Paraspinal muscular defects in Lfng segmentation mutant mice
The FASEB Journal, 2009
Activation of musculoskeletal development and repair mechanisms in the regenerating lizard tail (344.7)
The FASEB Journal, 2014
Uniquely among amniote vertebrates, lizards can lose their tails and regrow a functional replacem... more Uniquely among amniote vertebrates, lizards can lose their tails and regrow a functional replacement. These regenerated tails, which have an organization distinct from the original tail, contain ne...
Scientific Reports, 2020
Reptiles are the only amniotes that maintain the capacity to regenerate appendages. This study pr... more Reptiles are the only amniotes that maintain the capacity to regenerate appendages. This study presents the first anatomical and histological evidence of tail repair with regrowth in an archosaur, the American alligator. The regrown alligator tails constituted approximately 6–18% of the total body length and were morphologically distinct from original tail segments. Gross dissection, radiographs, and magnetic resonance imaging revealed that caudal vertebrae were replaced by a ventrally-positioned, unsegmented endoskeleton. This contrasts with lepidosaurs, where the regenerated tail is radially organized around a central endoskeleton. Furthermore, the regrown alligator tail lacked skeletal muscle and instead consisted of fibrous connective tissue composed of type I and type III collagen fibers. The overproduction of connective tissue shares features with mammalian wound healing or fibrosis. The lack of skeletal muscle contrasts with lizards, but shares similarities with regenerated t...
Hepatology, 2008
Alagille syndrome (AGS) is a heterogeneous developmental disorder associated with bile duct pauci... more Alagille syndrome (AGS) is a heterogeneous developmental disorder associated with bile duct paucity and various organ anomalies. The syndrome is caused by mutations in JAG1, which encodes a ligand in the Notch signaling pathway, in the majority of cases and mutations in the NOTCH2 receptor gene in less than 1% of patients. Although a wide array of JAG1 mutations have been identified in the AGS population, these mutational variants have not accounted for the wide phenotypic variability observed in patients with this syndrome. The Fringe genes encode glycosyltransferases, which modify Notch and alter ligand-receptor affinity. In this study, we analyzed double heterozygous mouse models to examine the Fringe genes as potential modifiers of the Notchmediated hepatic phenotype observed in AGS. We generated mice that were haploinsufficient for both Jag1 and one of three paralogous Fringe genes: Lunatic (Lfng), Radical (Rfng), and Manic (Mfng). Adult Jag1 ؉/؊ Lfng ؉/؊ and Jag1 ؉/؊ Rfng ؉/؊ mouse livers exhibited widespread bile duct proliferation beginning at 5 weeks of age and persisting up to 1 year. The Jag1 ؉/؊ Mfng ؉/؊ livers showed a subtle, yet significant increase in bile duct numbers and bile duct to portal tract ratios. These abnormalities were not observed in the newborn period. Despite the portal tract expansion by bile ducts, fibrosis was not increased and epithelial to mesenchymal transition was not shown in the affected portal tracts. Conclusion: Mice heterozygous for mutations in Jag1 and the Fringe genes display striking bile duct proliferation, which is not apparent at birth. These findings suggest that the Fringe genes may regulate postnatal bile duct growth and remodeling, and serve as candidate modifiers of the hepatic phenotype in AGS.
Developmental Biology, 2011
Developmental Biology, 2009
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Papers by Jeanne Wilson-Rawls