Jason R Jessen

Middle Tennessee State University, Murfreesboro, Tennessee, United States

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Publications (30)182.18 Total impact

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    ABSTRACT: During vertebrate gastrulation, convergence and extension movements elongate embryonic tissues anteroposteriorly and narrow them mediolaterally. Planar Cell Polarity (PCP) signaling is essential for mediolateral cell elongation underlying these movements, but how this polarity arises is poorly understood. We analyzed cell elongation, orientation, and migration behaviors of lateral mesodermal cells undergoing convergence and extension movements in wild-type embryos and mutants for the Wnt/PCP core component Trilobite/Vangl2. We demonstrate that Vangl2 function is required at the time when cells transition to a highly elongated and mediolaterally aligned body. We show that tri/vangl2 mutant cells fail to undergo this transition and to migrate along a straight path and high net speed towards the dorsal midline. Instead, tri/vangl2 mutant cells exhibit an anterior/animal pole bias in their cell body alignment and movement direction, suggesting that PCP signaling promotes effective dorsal migration in part by suppressing anterior/animalward cell polarity and movement. Endogenous Vangl2 protein accumulates at the plasma membrane of mesenchymal converging cells at the time its function is required for mediolaterally polarized cell behavior. Heterochronic cell transplantations demonstrated that Vangl2 cell membrane accumulation is stage dependent, and regulated by both intrinsic factors and an extracellular signal, which is distinct from PCP signaling or other gastrulation regulators, including BMP and Nodals. Moreover, mosaic expression of fusion proteins revealed enrichment of Vangl2 at the anterior cell edges of highly mediolaterally elongated cells, consistent with the PCP pathway core components' asymmetric distribution in Drosophila and vertebrate epithelia. © 2015. Published by The Company of Biologists Ltd.
    Development 06/2015; 142(14). DOI:10.1242/dev.119032 · 6.46 Impact Factor
  • Julia J Buckley · Jason R Jessen ·
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    ABSTRACT: Matrix metalloproteinases (MMPs), adamalysins, astacins, and serralysins are members of the metzincin superfamily of proteases. MMPs constitute a large protein family of both secreted and membrane-tethered enzymes that are synthesized as zymogens (proMMP) and activated by a cysteine-switch mechanism. First described over 50 years ago by Gross and Lapiere as a collagenolytic activity in amphibian tissues, the human MMP family now encompasses 23 different genes whose encoded proteins are capable of cleaving a variety of extracellular matrix protein substrates. Since their expression is upregulated in many cancer cell types, MMPs have received much attention particularly in the areas of tumor progression and metastasis. However, in terms of normal developmental processes, much less is known regarding MMP function and substrate identity. Data from knockout mouse studies support the notion that MMPs are not essential regulators of embryonic development, suggesting redundancy between MMPs or the presence of subtle phenotypes. However, studies on MMP function in other model systems indicate a larger role for MMP-dependent proteolysis during embryonic processes. Here, we review the current knowledge of MMPs from diverse model systems ranging from flowering plants and invertebrates to non-mammalian vertebrates.
    Frontiers in bioscience (Scholar edition) 06/2015; 7(1):168-183.
  • Jason R Jessen ·
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    ABSTRACT: The zebrafish extracellular matrix (ECM) is a dynamic and pleomorphic structure consisting of numerous proteins that together regulate a variety of cellular and morphogenetic events beginning as early as gastrulation. The zebrafish genome encodes a similar complement of ECM proteins as found in other vertebrate organisms including glycoproteins, fibrous proteins, proteoglycans, glycosaminoglycans, and interacting or modifying proteins such as integrins and matrix metalloproteinases. As a genetic model system combined with its amenability to high-resolution microscopic imaging, the zebrafish allows interrogation of ECM protein structure and function in both the embryo and adult. Accumulating data have identified important roles for zebrafish ECM proteins in processes as diverse as cell polarity, migration, tissue mechanics, organ laterality, muscle contraction, and regeneration. In this review, I highlight recently published data on these topics that demonstrate how the ECM proteins fibronectin, laminin, and collagen contribute to zebrafish development and adult homeostasis. Copyright © 2014. Published by Elsevier Inc.
    Developmental Biology 12/2014; 401(1). DOI:10.1016/j.ydbio.2014.12.022 · 3.55 Impact Factor
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    ABSTRACT: Zebrafish gastrulation cell movements occur in the context of dynamic changes in extracellular matrix (ECM) organization and require the concerted action of planar cell polarity (PCP) proteins that regulate cell elongation and mediolateral alignment. Data obtained using Xenopus laevis gastrulae have shown that integrin-fibronectin interactions underlie the formation of polarized cell protrusions necessary for PCP and have implicated PCP proteins themselves as regulators of ECM. By contrast, the relationship between establishment of PCP and ECM assembly/remodeling during zebrafish gastrulation is unclear. We previously showed that zebrafish embryos carrying a null mutation in the four-pass transmembrane PCP protein vang-like 2 (vangl2) exhibit increased matrix metalloproteinase activity and decreased immunolabeling of fibronectin. These data implicated for the first time a core PCP protein in the regulation of pericellular proteolysis of ECM substrates and raised the question of whether other zebrafish PCP proteins also impact ECM organization. In Drosophila melanogaster, the cytoplasmic PCP protein Prickle binds Van Gogh and regulates its function. Here we report that similar to vangl2, loss of zebrafish prickle1a decreases fibronectin protein levels in gastrula embryos. We further show that Prickle1a physically binds Vangl2 and regulates both the subcellular distribution and total protein level of Vangl2. These data suggest that the ability of Prickle1a to impact fibronectin organization is at least partly due to effects on Vangl2. In contrast to loss of either Vangl2 or Prickle1a function, we find that glypican4 (a Wnt co-receptor) and frizzled7 mutant gastrula embryos with disrupted non-canonical Wnt signaling exhibit the opposite phenotype, namely increased fibronectin assembly. Our data show that glypican4 mutants do not have decreased proteolysis of ECM substrates, but instead have increased cell surface cadherin protein expression and increased intercellular adhesion. These data indicate that Wnt/Glypican4/Frizzled signaling regulates ECM assembly through effects on cadherin-mediated cell cohesion. Together, our results demonstrate that zebrafish Vangl2/Prickle1a and non-canonical Wnt/Frizzled signaling have opposing effects on ECM organization underlying PCP and gastrulation cell movements.
    Developmental Biology 09/2013; 383(1). DOI:10.1016/j.ydbio.2013.08.027 · 3.55 Impact Factor
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    ABSTRACT: Matrix metalloproteinases (MMPs) are zinc-endopeptidases that play roles in numerous pathophysiological processes and therefore are promising drug targets. However, the large size of this family and a lack of highly selective compounds that can be used for imaging or inhibition of specific MMPs members has limited efforts to better define their biological function. Here we describe a protein engineering strategy coupled with small molecule probe design to selectively target individual members of the MMP family. Specifically, we introduce a cysteine residue near the active site of a selected protease that does not alter its overall activity or function but allows direct covalent modifi-cation by a small molecule probe containing a reactive electrophile. This specific engineered interaction between the probe and the target protease provides a means to both image and inhibit the modified protease with absolute specificity. Here we demonstrate the feasibility of the approach for two distinct MMP proteases, MMP-12 and MT1-MMP (MMP-14).
    Journal of the American Chemical Society 05/2013; 135(24). DOI:10.1021/ja403523p · 12.11 Impact Factor
  • Nathan A. Mundell · Jason R. Jessen ·
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    ABSTRACT: The importance of extracellular matrix proteins in the development of chick, frog, and mouse embryos has been recognized for decades. Accordingly, with the emergence of zebrafish as a genetic and developmental model system, there has been a steady increase in the number of studies showing developmental roles for matrix proteins, their receptors, and their modifying enzymes. The goal of this chapter is to highlight some of the extracellular matrix and interacting proteins present in the developing zebrafish embryo and discuss examples of morphogenetic processes requiring extracellular matrix protein expression, assembly, and turnover.
    Extracellular Matrix in Development, 01/2013: pages 187-218;
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    ABSTRACT: Understanding how planar cell polarity (PCP) is established, maintained, and coordinated in migrating cell populations is an important area of research with implications for both embryonic morphogenesis and tumor cell invasion. We recently reported that the PCP protein Vang-like 2 (VANGL2) regulates the endocytosis and cell surface level of membrane type-1 matrix metalloproteinase (MMP14 or MT1-MMP). Here, we further discuss these findings in terms of extracellular matrix (ECM) remodeling, cell migration, and zebrafish gastrulation. We also demonstrate that VANGL2 function impacts the focal degradation of ECM by human cancer cells including the formation or stability of invadopodia. Together, our findings implicate MMP14 as a downstream effector of VANGL2 signaling and suggest a model whereby the regulation of pericellular proteolysis is a fundamental aspect of PCP in migrating cells.
    Communicative & integrative biology 07/2012; 5(4):325-8. DOI:10.4161/cib.20291
  • Rachel E Quick · Julie A Dunlap · Jason R Jessen ·
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    ABSTRACT: Membrane tethered matrix metalloproteinases (MMPs) cleave a variety of extracellular matrix (ECM) and non-ECM targets and play important roles during embryonic development and tumor progression. Membrane tethered MMPs in particular are important regulators of both tissue invasion and morphogenesis. Much attention has been given to understanding the function of human and mouse MMP14 (also called membrane type-1 MMP, MT1-MMP) and our own data have linked zebrafish Mmp14 to the regulation of gastrulation cell movements. However, less is known regarding the expression and function of other membrane tethered MMPs. We report the cloning and gene expression analysis of zebrafish mmp15a and mmp15b (MT2-MMP) during early embryonic and larval development. Our data show that mmp15a exhibits limited expression prior to segmentation stages and is first detected in the tectum and posterior tailbud. At 24hours post-fertilization (hpf) mmp15a localizes to the caudal hematopoietic tissue, pectoral fin buds, and mandibular arch. By contrast, mmp15b is strongly expressed during gastrula stages before becoming restricted to the polster and anterior neural plate. From 24 to 48hpf, mmp15b expression is detected in the pharyngeal arches, fin buds, otic vesicle, pronephric ducts, proctodeum, tail epidermis, posterior lateral line primordia, and caudal notochord. During the larval period beginning at 72hpf, mmp15b expression becomes restricted to the brain ventricular zone, pharyngeal arches, pectoral fins, and the proctodeum. Many of the mmp15-expressing tissues have been shown to express genes encoding components of the ECM including collagens, fibronectin, and laminins. Our data thus provide a foundation for uncovering the role of Mmp15-dependent pericellular proteolysis during zebrafish embryonic development.
    Gene Expression Patterns 06/2012; 12(7-8):254-60. DOI:10.1016/j.gep.2012.05.003 · 1.38 Impact Factor
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    ABSTRACT: Planar cell polarity (PCP) describes the polarized orientation of cells within the plane of a tissue. Unlike epithelial PCP, the mechanisms underlying PCP signaling in migrating cells remain undefined. Here, the establishment of PCP must be coordinated with dynamic changes in cell adhesion and extracellular matrix (ECM) organization. During gastrulation, the membrane type-1 matrix metalloproteinase (MT1-MMP or MMP14) is required for PCP and convergence and extension cell movements. We report that the PCP protein Vang-like 2 (VANGL2) regulates the endocytosis and cell-surface availability of MMP14 in manner that is dependent on focal adhesion kinase. We demonstrate that zebrafish trilobite/vangl2 mutant embryos exhibit increased Mmp14 activity and decreased ECM. Furthermore, in vivo knockdown of Mmp14 partially rescues the Vangl2 loss-of-function convergence and extension phenotype. This study identifies a mechanism linking VANGL2 with MMP14 trafficking and suggests that establishment of PCP in migrating gastrula cells requires regulated proteolytic degradation or remodeling of the ECM. Our findings implicate matrix metalloproteinases as downstream effectors of PCP and suggest a broadly applicable mechanism whereby VANGL2 affects diverse morphogenetic processes.
    Journal of Cell Science 02/2012; 125(Pt 9):2141-7. DOI:10.1242/jcs.097964 · 5.43 Impact Factor
  • Jason R Jessen ·
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    ABSTRACT: Planar cell polarity was first described in invertebrates over 20 years ago and is defined as the polarity of cells (and cell structures) within the plane of a tissue, such as an epithelium. Studies in the last 10 years have identified critical roles for vertebrate homologs of these planar cell polarity proteins during gastrulation cell movements. In zebrafish, the terms convergence and extension are used to describe the collection of morphogenetic movements and cell behaviors that contribute to narrowing and elongation of the embryonic body plan. Disruption of planar cell polarity gene function causes profound defects in convergence and extension creating an embryo that has a shortened anterior-posterior axis and is broadened mediolaterally. The zebrafish gastrula-stage embryo is transparent and amenable to live imaging using both Nomarski/differential interference contrast and fluorescence microscopy. This chapter describes methods to analyze convergence and extension movements at the cellular level and thereby connect embryonic phenotypes with underlying planar cell polarity defects in migrating cells.
    Methods in molecular biology (Clifton, N.J.) 01/2012; 839:69-78. DOI:10.1007/978-1-61779-510-7_6 · 1.29 Impact Factor
  • Andrew Latimer · Jason R. Jessen ·
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    ABSTRACT: Zebrafish gastrulation entails morphogenetic cell movements that shape the body plan and give rise to an embryo with defined anterior–posterior and dorsal–ventral axes. Regulating these cell movements are diverse signaling pathways and proteins including Wnts, Src-family tyrosine kinases, cadherins, and matrix metalloproteinases. While our knowledge of how these proteins impact cell polarity and migration has advanced considerably in the last decade, almost no data exist regarding the organization of extracellular matrix (ECM) during zebrafish gastrulation. Here, we describe for the first time the assembly of a fibronectin (FN) and laminin containing ECM in the early zebrafish embryo. This matrix was first detected at early gastrulation (65% epiboly) in the form of punctae that localize to tissue boundaries separating germ layers from each other and the underlying yolk cell. Fibrillogenesis increased after mid-gastrulation (80% epiboly) coinciding with the period of planar cell polarity pathway-dependent convergence and extension cell movements. We demonstrate that FN fibrils present beneath deep mesodermal cells are aligned in the direction of membrane protrusion formation. Utilizing antisense morpholino oligonucleotides, we further show that knockdown of FN expression causes a convergence and extension defect. Taken together, our data show that similar to amphibian embryos, the formation of ECM in the zebrafish gastrula is a dynamic process that occurs in parallel to at least a portion of the polarized cell behaviors shaping the embryonic body plan. These results provide a framework for uncovering the interrelationship between ECM structure and cellular processes regulating convergence and extension such as directed migration and mediolateral/radial intercalation.
    Matrix biology: journal of the International Society for Matrix Biology 03/2010; 29(2-29):89-96. DOI:10.1016/j.matbio.2009.10.002 · 5.07 Impact Factor
  • V Ashley Cantrell · Jason R Jessen ·
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    ABSTRACT: Van Gogh-Like 2 (VANGL2) is a planar cell polarity protein essential for collective migration during embryonic development, yet its contribution to tumor cell motility and invasion are unknown. We report for the first time that loss of VANGL2 in human cancer cells promotes efficient collective and directed migration and matrix metalloproteinase (MMP)-dependent ECM invasion. We show that VANGL2 knockdown cells exhibit increased activation of secreted MMP2, higher levels of membrane-localized MMP14, and decreased cell-surface fibronectin. These important findings support the notion that planar cell polarity proteins act in coordination with known regulators of cancer cell migration to influence invasion and perhaps metastasis.
    Cancer letters 08/2009; 287(1):54-61. DOI:10.1016/j.canlet.2009.05.041 · 5.62 Impact Factor
  • Jason R Jessen ·
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    ABSTRACT: For almost 15 years, the concept that noncanonical (beta-catenin-independent) Wnt signaling pathways play key roles in embryonic development has grown steadily in the scientific literature. Significant progress has been made toward understanding how these pathways regulate morphogenetic processes as diverse as gastrulation cell movements and the formation of cilia. More recently, however, data have implicated components of noncanonical Wnt/Ca(2+) and Wnt/planar cell polarity signaling in directly promoting the invasiveness and malignant progression of diverse forms of human cancer. Here I review this emerging field of cancer research using data from developmental model systems to provide a framework for addressing future questions.
    Zebrafish 04/2009; 6(1):21-8. DOI:10.1089/zeb.2008.0571 · 1.95 Impact Factor
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    ABSTRACT: Phospholipase D (PLD) hydrolyzes phosphatidylcholine to generate phosphatidic acid and choline. Studies in cultured cells and Drosophila melanogaster have implicated PLD in the regulation of many cellular functions, including intracellular vesicle trafficking, cell proliferation and differentiation. However, the function of PLD in vertebrate development has not been explored. Here we report cloning and characterization of a zebrafish PLD1 (pld1) homolog. Like mammalian PLDs, zebrafish Pld1 contains two conservative HKD motifs. Maternally contributed pld1 transcripts are uniformly distributed in early embryo. Localized expression of pld1 is observed in the notochord during early segmentation, in the somites during later segmentation and in the liver at the larval stages. Studies in intact and cell-free preparations demonstrate evolutionary conservation of regulation. Inhibition of Pld1 expression using antisense morpholino oligonucleotides (MO) interfering with the translation or splicing of pld1 impaired intersegmental vessel (ISV) development. Incubating embryos with 1-butanol, which diverts production of phosphatidic acid to a phosphatidylalcohol, caused similar ISV defects. To determine where Pld1 is required for ISV development we performed transplantation experiments. Analyses of the mosaic Pld1 deficient embryos showed partial suppression of ISV defects in the segments containing transplanted wild-type notochord cells but not in the ones containing wild-type somitic cells. These results provide the first evidence that function of Pld1 in the developing notochord is essential for vascular development in vertebrates.
    Developmental Biology 03/2009; 328(2):363-76. DOI:10.1016/j.ydbio.2009.01.035 · 3.55 Impact Factor
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    Andrew J Latimer · Jason R Jessen ·
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    ABSTRACT: Hepatocyte growth factor (HGF) and its receptor tyrosine kinase Met are linked to several processes underlying vertebrate development and cancer progression. Here, we characterized the expression of zebrafish c-met, hgf1, and hgf2 from cleavage stages through organogenesis and initiated an analysis of Met signaling. We identified c-met as a marker of endoderm and demonstrated that its expression can be activated downstream of Nodal. Injection of c-met mRNA drives expression of the endodermal gene sox17. During gastrulation, hgf1 transcripts are visible in mesendodermal cells along the midline. Later, c-met is expressed in kidney, islet2-positive neurons, and liver. We show that hgf1 is transcribed during gastrulation while hgf1 and hgf2 are detectable in pharyngeal arches and swim bladder. Similar to mouse, knockdown of zebrafish Met reduces liver size. Our results suggest a role for Met during endoderm specification and indicate that mechanisms of liver development are conserved between mammals and bony fish.
    Developmental Dynamics 12/2008; 237(12):3904-15. DOI:10.1002/dvdy.21794 · 2.38 Impact Factor
  • Rebecca C Coyle · Andrew Latimer · Jason R Jessen ·
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    ABSTRACT: Key to invasiveness is the ability of tumor cells to modify the extracellular matrix, become motile, and engage in directed migration towards the vasculature. One significant protein associated with metastatic progression is membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP14). How MMP14 activity is coordinated with other signaling pathways to regulate cell migration in vivo is largely unknown. Here we have used zebrafish embryogenesis as a model to understand the potential relationship between MMP14-dependent pericellular proteolysis, cell polarity, and motility. Knockdown of zebrafish Mmp14 function disrupted gastrulation convergence and extension cell movements and craniofacial morphogenesis. Using time-lapse imaging and morphometric analyses, we show that Mmp14 is required for proper cell polarity underlying the directed migration of mesodermal cells during gastrulation. We have identified a genetic interaction between mmp14 and non-canonical Wnt signaling, a pathway that also regulates cell polarity in embryonic tissues and is increasingly being linked with tumor cell migration. Finally, we demonstrate that Van Gogh-like 2, a key regulator of the non-canonical Wnt pathway, co-localizes with MMP14 and becomes redistributed towards the leading edge of polarized human cancer cells. Together, our results support the notion that pathways regulating pericellular proteolysis and cell polarity converge to promote efficient cell migration.
    Experimental Cell Research 07/2008; 314(10):2150-62. DOI:10.1016/j.yexcr.2008.03.010 · 3.25 Impact Factor
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    ABSTRACT: We have identified 645,088 candidate polymorphisms in zebrafish and observe a single nucleotide polymorphism (SNP) validation rate of 71% to 86%, improving with polymorphism confidence score. Variant sites are non-random, with an excess of specific novel T- and A-rich motifs. We positioned half of the polymorphisms on zebrafish genetic and physical maps as a resource for positional cloning. We further demonstrate bulked segregant analysis using the anchored SNPs as a method for high-throughput genetic mapping in zebrafish.
    Genome biology 04/2007; 8(4):R55. DOI:10.1186/gb-2007-8-4-r55 · 10.81 Impact Factor
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    ABSTRACT: Human ARHGEF11, a PDZ-domain-containing Rho guanine nucleotide exchange factor (RhoGEF), has been studied primarily in tissue culture, where it exhibits transforming ability, associates with and modulates the actin cytoskeleton, regulates neurite outgrowth, and mediates activation of Rho in response to stimulation by activated Galpha12/13 or Plexin B1. The fruit fly homolog, RhoGEF2, interacts with heterotrimeric G protein subunits to activate Rho, associates with microtubules, and is required during gastrulation for cell shape changes that mediate epithelial folding. Here, we report functional characterization of a zebrafish homolog of ARHGEF11 that is expressed ubiquitously at blastula and gastrula stages and is enriched in neural tissues and the pronephros during later embryogenesis. Similar to its human homolog, zebrafish Arhgef11 stimulated actin stress fiber formation in cultured cells, whereas overexpression in the embryo of either the zebrafish or human protein impaired gastrulation movements. Loss-of-function experiments utilizing a chromosomal deletion that encompasses the arhgef11 locus, and antisense morpholino oligonucleotides designed to block either translation or splicing, produced embryos with ventrally-curved axes and a number of other phenotypes associated with ciliated epithelia. Arhgef11-deficient embryos often exhibited altered expression of laterality markers, enlarged brain ventricles, kidney cysts, and an excess number of otoliths in the otic vesicles. Although cilia formed and were motile in these embryos, polarized distribution of F-actin and Na(+)/K(+)-ATPase in the pronephric ducts was disturbed. Our studies in zebrafish embryos have identified new, essential roles for this RhoGEF in ciliated epithelia during vertebrate development.
    Development 04/2007; 134(5):921-31. DOI:10.1242/dev.02776 · 6.46 Impact Factor
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    Jason R Jessen · Lila Solnica-Krezel ·
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    ABSTRACT: Despite structural differences between species, highly conserved mechanisms pattern the early vertebrate embryo into an animal with clearly defined anteroposterior and dorsoventral axes. Years of research have demonstrated that dorsoventral polarity in the amphibian embryo is established in large part through the concerted action of specific signaling molecules and microtubule-mediated transport mechanisms that enrich these molecules on the dorsal side of the embryo (see review by Weaver and Kimelman [2004]). A critical protein with dorsalizing activity in both frog and fish embryos is β-catenin, a component of the canonical Wnt signaling cascade. It has been shown that manipulation of β-catenin levels in Xenopus embryos dramatically affects axis formation (Heasman et al., 1994 and Funayama et al., 1995). In the canonical Wnt pathway, the ability of β-catenin to act as a transcriptional coactivator is restricted by a destruction complex, a group of cytoplasmic proteins (Axin, Adenomatous Polyposis Coli, Glycogen Synthase Kinase 3β, and others), whose function is to mark β-catenin for ubiquitination and degradation (see review by Logan and Nusse [2004]). Normally, Wnt ligand binding to a Frizzled transmembrane receptor activates a signaling cascade that disrupts this protein complex and results in accumulation of unphosphorylated β-catenin (Figure 1). β-catenin then enters the nucleus and forms complexes with TCF/LEF transcription factors to activate the transcription of target genes. However, there has been growing consensus among researchers that, during Xenopus axis formation, a Wnt ligand is not involved and that an unidentified molecule with dorsalizing activity regulates downstream components of canonical Wnt signaling to influence β-catenin stabilization (Weaver and Kimelman [2004]; also see zebrafish data discussed below).
    Cell 04/2005; 120(6):736-7. DOI:10.1016/j.cell.2005.03.005 · 32.24 Impact Factor
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    ABSTRACT: Gata2 is an essential hematopoietic transcriptional factor that is also expressed prominently in the nervous system. The early lethality of knockout mice due to severe anemia has largely precluded studies of gata2 neural regulation and function. In this report, we describe the identification of zebrafish Pur alpha and Sp8 orthologs as two factors that function to regulate neuronal expression of gata2. During embryogenesis, Pur alpha is expressed widely, whereas Sp8 has an overlapping pattern of expression with gata2 in the nervous system. Knockdown and ectopic expressions of Pur alpha and Sp8 indicate that these factors function, respectively, as a repressor and an activator of gata2 gene expression in the nervous system. With consideration given to the previously established roles for these factors, we propose a model for how the transcriptional regulation of neural gata2 expression may be involved in controlling cellular proliferation in the nervous system.
    Developmental Biology 12/2004; 275(1):225-34. DOI:10.1016/j.ydbio.2004.08.007 · 3.55 Impact Factor

Publication Stats

1k Citations
182.18 Total Impact Points


  • 2015
    • Middle Tennessee State University
      • Department of Biology
      Murfreesboro, Tennessee, United States
  • 2002-2013
    • Vanderbilt University
      • • Department of Medicine
      • • Department of Cancer Biology
      • • Department of Biological Sciences
      Нашвилл, Michigan, United States
  • 2004
    • University of California, Los Angeles
      • Department of Molecular, Cell, and Developmental Biology (MCDB)
      Los Angeles, CA, United States
  • 1997-2003
    • Georgia Health Sciences University
      • • Institute of Molecular Medicine and Genetics
      • • Department of Biochemistry & Molecular Biology
      Augusta, Georgia, United States