707 results match your criteria factors morphogens

Two-Phase Lineage Specification of Telencephalon Progenitors Generated From Mouse Embryonic Stem Cells.

Front Cell Dev Biol 2021 16;9:632381. Epub 2021 Apr 16.

Department of Brain Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.

Proper brain development requires precisely controlled phases of stem cell proliferation, lineage specification, differentiation, and migration. Lineage specification depends partly on concentration gradients of chemical cues called morphogens. However, the rostral brain (telencephalon) expands prominently during embryonic development, dynamically altering local morphogen concentrations, and telencephalic subregional properties develop with a time lag. Read More

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Colonic epithelial adaptation to EGFR-independent growth induces chromosomal instability and is accelerated by prior injury.

Neoplasia 2021 Apr 23;23(5):488-501. Epub 2021 Apr 23.

Department of Pathology, Division of GI/Liver Pathology, Johns Hopkins University School of Medicine, Baltimore, MD USA; Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD USA. Electronic address:

Although much is known about the gene mutations required to drive colorectal cancer (CRC) initiation, the tissue-specific selective microenvironments in which neoplasia arises remains less characterized. Here, we determined whether modulation of intestinal stem cell niche morphogens alone can exert a neoplasia-relevant selective pressure on normal colonic epithelium. Using adult stem cell-derived murine colonic epithelial organoids (colonoids), we employed a strategy of sustained withdrawal of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) inhibition to select for and expand survivors. Read More

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Three-Dimensional Human Neural Stem Cell Models to Mimic Heparan Sulfate Proteoglycans and the Neural Niche.

Semin Thromb Hemost 2021 Apr 1;47(3):308-315. Epub 2021 Apr 1.

Genomics Research Centre, Stem Cell and Neurogenesis Group, Centre for Genomics and Personalised Health, School of Biomedical Science, Queensland University of Technology, Kelvin Grove, Queensland, Australia.

Heparan sulfate proteoglycans (HSPGs) are a diverse family of polysaccharides, consisting of a core protein with glycosaminoglycan (GAG) side chains attached. The heterogeneous GAG side-chain carbohydrates consist of repeating disaccharides, with each side chain possessing a specific sulfation pattern. It is the variable sulfation pattern that allows HSPGs to interact with numerous ligands including growth factors, cytokines, chemokines, morphogens, extracellular matrix (ECM) glycoproteins, collagens, enzymes, and lipases. Read More

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The essential role of primary cilia in cerebral cortical development and disorders.

Curr Top Dev Biol 2021 25;142:99-146. Epub 2021 Jan 25.

UNC Neuroscience Center and the Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, NC, United States. Electronic address:

Primary cilium, first described in the 19th century in different cell types and organisms by Alexander Ecker, Albert Kolliker, Aleksandr Kowalevsky, Paul Langerhans, and Karl Zimmermann (Ecker, 1844; Kolliker, 1854; Kowalevsky, 1867; Langerhans, 1876; Zimmermann, 1898), play an essential modulatory role in diverse aspects of nervous system development and function. The primary cilium, sometimes referred to as the cell's 'antennae', can receive wide ranging inputs from cellular milieu, including morphogens, growth factors, neuromodulators, and neurotransmitters. Its unique structural and functional organization bequeaths it the capacity to hyper-concentrate signaling machinery in a restricted cellular domain approximately one-thousandth the volume of cell soma. Read More

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January 2021

The foggy world(s) of p63 isoform regulation in normal cells and cancer.

J Pathol 2021 Feb 26. Epub 2021 Feb 26.

Research Centre of Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer Institute, Brno, Czech Republic.

The p53 family member p63 exists as two major protein variants (TAp63 and ΔNp63) with distinct expression patterns and functional properties. Whilst downstream target genes of p63 have been studied intensively, how p63 variants are themselves controlled has been relatively neglected. Here, we review advances in understanding ΔNp63 and TAp63 regulation, highlighting their distinct pathways. Read More

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February 2021

Morphogens and growth factor signalling in the myeloma bone-lining niche.

Cell Mol Life Sci 2021 Feb 11. Epub 2021 Feb 11.

Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.

Multiple myeloma is a malignancy caused by the clonal expansion of abnormal plasma cells. Myeloma cells have proven to be incredibly successful at manipulating their microenvironment to promote growth and to evade modern therapies. They have evolved to utilise the integral signalling pathways of the bone and bone marrow to drive disease progression. Read More

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February 2021

Extrinsic Regulators of mRNA Translation in Developing Brain: Story of WNTs.

Cells 2021 Jan 28;10(2). Epub 2021 Jan 28.

Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA.

Extrinsic molecules such as morphogens can regulate timed mRNA translation events in developing neurons. In particular, Wingless-type MMTV integration site family, member 3 (Wnt3), was shown to regulate the translation of mRNA encoding a Forkhead transcription factor P2 in the neocortex. However, the Wnt receptor that possibly mediates these translation events remains unknown. Read More

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January 2021

A Systems View of the Heparan Sulfate Interactome.

J Histochem Cytochem 2021 Feb;69(2):105-119

Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California.

Heparan sulfate proteoglycans consist of a small family of proteins decorated with one or more covalently attached heparan sulfate glycosaminoglycan chains. These chains have intricate structural patterns based on the position of sulfate groups and uronic acid epimers, which dictate their ability to engage a large repertoire of heparan sulfate-binding proteins, including extracellular matrix proteins, growth factors and morphogens, cytokines and chemokines, apolipoproteins and lipases, adhesion and growth factor receptors, and components of the complement and coagulation system. This review highlights recent progress in the characterization of the so-called "heparan sulfate interactome," with a major focus on systems-wide strategies as a tool for discovery and characterization of this subproteome. Read More

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February 2021

Dynamic patterning by morphogens illuminated by cis-regulatory studies.

Development 2021 01 20;148(2). Epub 2021 Jan 20.

California Institute of Technology, Division of Biology and Biological Engineering, 1200 East California Blvd., Pasadena, CA 91125, USA

Morphogen concentration changes in space as well as over time during development. However, how these dynamics are interpreted by cells to specify fate is not well understood. Here, we focus on two morphogens: the maternal transcription factors Bicoid and Dorsal, which directly regulate target genes to pattern embryos. Read More

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January 2021

Expression of syndecan-1 in oral cavity squamous cell carcinoma.

J Histotechnol 2021 Mar 24;44(1):46-51. Epub 2020 Dec 24.

Department of Pathology, Wrocław Medical University, Wrocław, Poland.

Syndecan-1 (SDC1) belongs to heparan sulfate proteoglycans which may interact with different growth factors, cytokines, morphogens and promote tumor growth and invasion. The aim of the present study was to assess the immunohistochemical expression of syndecan-1 in oral squamous cell carcinoma (OSCC) and oral cysts. Evaluation of the staining pattern with the clinico-histological characteristics of patients was performed. Read More

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Reconstitution of Morphogen Signaling Gradients in Cultured Cells.

Methods Mol Biol 2021 ;2258:43-56

Whitehead Institute for Biomedical Research, Cambridge, MA, USA.

Development of multicellular organisms depends on the proper establishment of signaling information in space and time. Secreted molecules called morphogens form concentration gradients in space and provide positional information to differentiating cells within the organism. Although the key molecular components of morphogen pathways have been identified, how the architectures and key parameters of morphogen pathways control the properties of signaling gradients, such as their size, speed, and robustness to perturbations, remains challenging to study in developing embryos. Read More

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Development and optimization of a personalized fibrin membrane derived from the plasma rich in growth factors technology.

Exp Eye Res 2021 02 14;203:108402. Epub 2020 Dec 14.

Instituto Oftalmológico Fernández-Vega. Fundación de Investigación Oftalmológica. Universidad de Oviedo, Oviedo, Spain.

Purpose: To develop and characterize a new type of plasma rich in growth factors (PRGF) membrane for patients in which immune system is involved in the disease etiology.

Methods: Blood from three healthy donors was collected to obtain the different fibrin membranes by PRGF technology. PRGF obtained volumes were activated and divided into two groups: PRGF membrane (mPRGF) obtained after incubation at 37 °C for 30 min (control); and is-mPRGF: mPRGF obtained after incubation for 30 min at 56 °C. Read More

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February 2021

Heparan Sulfate Proteoglycans Can Promote Opposite Effects on Adhesion and Directional Migration of Different Cancer Cells.

J Med Chem 2020 12 7;63(24):15997-16011. Epub 2020 Dec 7.

Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.

Heparan sulfate proteoglycans take part in crucial events of cancer progression, such as epithelial-mesenchymal transition, cell migration, and cell invasion. Through sulfated groups on their glycosaminoglycan chains, heparan sulfate proteoglycans interact with growth factors, morphogens, chemokines, and extracellular matrix (ECM) proteins. The amount and position of sulfated groups are highly variable, thus allowing differentiated ligand binding and activity of heparan sulfate proteoglycans. Read More

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December 2020

The Polycomb group protein Ring1 regulates dorsoventral patterning of the mouse telencephalon.

Nat Commun 2020 11 11;11(1):5709. Epub 2020 Nov 11.

Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Dorsal-ventral patterning of the mammalian telencephalon is fundamental to the formation of distinct functional regions including the neocortex and ganglionic eminence. While Bone morphogenetic protein (BMP), Wnt, and Sonic hedgehog (Shh) signaling are known to determine regional identity along the dorsoventral axis, how the region-specific expression of these morphogens is established remains unclear. Here we show that the Polycomb group (PcG) protein Ring1 contributes to the ventralization of the mouse telencephalon. Read More

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November 2020

Cell-surface heparan sulfate proteoglycans as multifunctional integrators of signaling in cancer.

Cell Signal 2021 Jan 3;77:109822. Epub 2020 Nov 3.

Department of Gynecology and Obstetrics, Münster University Hospital, Münster, Germany. Electronic address:

Proteoglycans (PGs) represent a large proportion of the components that constitute the extracellular matrix (ECM). They are a diverse group of glycoproteins characterized by a covalent link to a specific glycosaminoglycan type. As part of the ECM, heparan sulfate (HS)PGs participate in both physiological and pathological processes including cell recruitment during inflammation and the promotion of cell proliferation, adhesion and motility during development, angiogenesis, wound repair and tumor progression. Read More

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January 2021

Interpretation of morphogen gradients by a synthetic bistable circuit.

Nat Commun 2020 11 2;11(1):5545. Epub 2020 Nov 2.

Microsoft Research, 21 Station Road, Cambridge, CB1 2FB, UK.

During development, cells gain positional information through the interpretation of dynamic morphogen gradients. A proposed mechanism for interpreting opposing morphogen gradients is mutual inhibition of downstream transcription factors, but isolating the role of this specific motif within a natural network remains a challenge. Here, we engineer a synthetic morphogen-induced mutual inhibition circuit in E. Read More

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November 2020

hedgehog can act as a morphogen in the absence of regulated Ci processing.

Elife 2020 10 21;9. Epub 2020 Oct 21.

Department of Biological Sciences, Columbia University, New York, United States.

Extracellular Hedgehog (Hh) proteins induce transcriptional changes in target cells by inhibiting the proteolytic processing of full-length Ci or mammalian Gli proteins to nuclear transcriptional repressors and by activating the full-length Ci or Gli proteins. We used Ci variants expressed at physiological levels to investigate the contributions of these mechanisms to dose-dependent Hh signaling in wing imaginal discs. Ci variants that cannot be processed supported a normal pattern of graded target gene activation and the development of adults with normal wing morphology, when supplemented by constitutive Ci repressor, showing that Hh can signal normally in the absence of regulated processing. Read More

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October 2020

Cerebellar Differentiation from Human Stem Cells Through Retinoid, Wnt, and Sonic Hedgehog Pathways.

Tissue Eng Part A 2020 Oct 1. Epub 2020 Oct 1.

Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, USA.

Differentiating cerebellar organoids can be challenging due to complex cell organization and structure in the cerebellum. Different approaches were investigated to recapitulate differentiation process of the cerebellum from human-induced pluripotent stem cells (hiPSCs) without high efficiency. This study was carried out to test the hypothesis that the combination of different signaling factors including retinoic acid (RA), Wnt activator, and sonic hedgehog (SHH) activator promotes the cerebellar differentiation of hiPSCs. Read More

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October 2020

Aggrecan, the Primary Weight-Bearing Cartilage Proteoglycan, Has Context-Dependent, Cell-Directive Properties in Embryonic Development and Neurogenesis: Aggrecan Glycan Side Chain Modifications Convey Interactive Biodiversity.

Biomolecules 2020 08 27;10(9). Epub 2020 Aug 27.

Raymond Purves Laboratory, Institute of Bone and Joint Research, Kolling Institute of Medical Research, Northern Sydney Local Health District, Royal North Shore Hospital, St. Leonards 2065, NSW, Australia.

This review examines aggrecan's roles in developmental embryonic tissues, in tissues undergoing morphogenetic transition and in mature weight-bearing tissues. Aggrecan is a remarkably versatile and capable proteoglycan (PG) with diverse tissue context-dependent functional attributes beyond its established role as a weight-bearing PG. The aggrecan core protein provides a template which can be variably decorated with a number of glycosaminoglycan (GAG) side chains including keratan sulphate (KS), human natural killer trisaccharide (HNK-1) and chondroitin sulphate (CS). Read More

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Synergistic interaction of hTGF-β with hBMP-6 promotes articular cartilage formation in chitosan scaffolds with hADSCs: implications for regenerative medicine.

BMC Biotechnol 2020 08 27;20(1):48. Epub 2020 Aug 27.

Department of Orthopaedics, Physical Medicine and Rehabilitation, University Hospital of Munich, 81377, Munich, Germany.

Background: Human TGF-β has been used in many studies to induce genes coding for typical cartilage matrix components and accelerate chondrogenic differentiation, making it the standard constituent in most cultivation media used for the assessment of chondrogenesis associated with various stem cell types on carrier matrices. However, in vivo data suggests that TGF-β and its other isoforms also induce endochondral and intramembranous osteogenesis in non-primate species to other mammals. Based on previously demonstrated improved articular cartilage induction by a using hTGF-β and hBMP-6 together on hADSC cultures and the interaction of TGF- β with matrix in vivo, the present study investigates the interaction of a chitosan scaffold as polyanionic polysaccharide with both growth factors. Read More

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Washed Equine Platelet Extract as an Anti-Inflammatory Biologic Pharmaceutical.

Tissue Eng Part A 2020 Sep 30. Epub 2020 Sep 30.

Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.

Mammalian platelets participate in the immediate tissue injury response by initiating coagulation and further promoting tissue injury mitigation and repair. The latter properties are deployed following platelet release of presynthetized morphogens, cytokines, and growth and chemotactic factors, which launch a tissue regenerative, angiogenic, and anti-inflammatory program. Several blood-derived biologic products, like platelet-rich plasma (PRP) and platelet lysate (PL), are currently on the market to allow proper healing and tissue regeneration. Read More

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September 2020

Airinemes: thin cellular protrusions mediate long-distance signalling guided by macrophages.

Dae Seok Eom

Open Biol 2020 08 19;10(8):200039. Epub 2020 Aug 19.

Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA.

Understanding the mechanisms of cell-to-cell communication is one of the fundamental questions in biology and medicine. In particular, long-range signalling where cells communicate over several cell diameters is vital during development and homeostasis. The major morphogens, their receptors and intracellular signalling cascades have largely been identified; however, there is a gap in our knowledge of how such signalling factors are propagated over a long distance. Read More

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Radixin Relocalization and Nonmuscle -Actinin Expression Are Features of Remodeling Cardiomyocytes in Adult Patients with Dilated Cardiomyopathy.

Dis Markers 2020 22;2020:9356738. Epub 2020 Jul 22.

Department of Cardiac Surgery, Kerckhoff Heart Center, Benekestrasse 2-8, Bad Nauheim 61231, Germany.

Background: Pediatric patients show an impressive capacity of cardiac regeneration. In contrast, severely deteriorated adult hearts do usually not recover. Since cardiac remodeling-involving the expression of fetal genes-is regarded as an adaptation to stress, we compared hearts of adult patients suffering from dilated cardiomyopathy (DCM) with remodeling of cultured neonatal (NRC) as well as adult (ARC) rat cardiomyocytes and the developing postnatal myocardium. Read More

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Glycosaminoglycan-Protein Interactions: The First Draft of the Glycosaminoglycan Interactome.

J Histochem Cytochem 2021 Feb 6;69(2):93-104. Epub 2020 Aug 6.

Univ Lyon, University Claude Bernard Lyon 1, CNRS, INSA Lyon, CPE, Institute of Molecular and Supramolecular Chemistry and Biochemistry, UMR 5246, Villeurbanne Cedex, France.

The six mammalian glycosaminoglycans (GAGs), chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate, hyaluronan, and keratan sulfate, are linear polysaccharides. Except for hyaluronan, they are sulfated to various extent, and covalently attached to proteins to form proteoglycans. GAGs interact with growth factors, morphogens, chemokines, extracellular matrix proteins and their bioactive fragments, receptors, lipoproteins, and pathogens. Read More

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February 2021

Cerebellar Morphology and Behavioral Profiles in Mice Lacking Heparan Sulfate Gene Function.

J Dev Biol 2020 Jul 11;8(3). Epub 2020 Jul 11.

Institute of Physiological Chemistry and Pathobiochemistry, Westfälische Wilhelms-Universität Münster, 48149 Münster, Germany.

Disruption of the Heparan sulfate (HS)-biosynthetic gene N-acetylglucosamine N-Deacetylase/N-sulfotransferase 1 () during nervous system development causes malformations that are composites of those caused by mutations of multiple HS binding growth factors and morphogens. However, the role of function in adult brain physiology is less explored. Therefore, we generated mice bearing a Purkinje-cell-specific deletion in gene function by using Cre/loxP technology under the control of the Purkinje cell protein 2 (Pcp2/L7) promotor, which results in HS undersulfation. Read More

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The Role of Glypicans in Cancer Progression and Therapy.

J Histochem Cytochem 2020 12 6;68(12):841-862. Epub 2020 Jul 6.

Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Glypicans are a family of heparan sulfate proteoglycans that are attached to the cell membrane via a glycosylphosphatidylinositol anchor. Glypicans interact with multiple ligands, including morphogens, growth factors, chemokines, ligands, receptors, and components of the extracellular matrix through their heparan sulfate chains and core protein. Therefore, glypicans can function as coreceptors to regulate cell proliferation, cell motility, and morphogenesis. Read More

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December 2020

GDF5 induces TBX3 in a concentration dependent manner - on a gold nanoparticle gradient.

Heliyon 2020 Jun 10;6(6):e04133. Epub 2020 Jun 10.

Institute of Biomedicine at Sahlgrenska Academy, Department of Clinical Chemistry and Transfusion Medicine, University of Gothenburg, Gothenburg, SE-413 45, Sweden.

Organs and tissues, such as cartilage and limbs, are formed during development through an orchestration of growth factors that function as morphogens. Examples of growth factors include growth differentiation factor 5 (GDF5) and transforming growth factors beta 1 and 3 (TGFβ-1 and TGFβ-3) which can specify creation of more than one cell type after forming a concentration gradient . Here, we studied the impact of morphogen gradients during differentiation of induced pluripotent stem cells (iPSCs) into the chondrocyte lineage. Read More

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Proximo-distal positional information encoded by an Fgf-regulated gradient of homeodomain transcription factors in the vertebrate limb.

Sci Adv 2020 Jun 3;6(23):eaaz0742. Epub 2020 Jun 3.

Cardiovascular Development Program, Centro Nacional de Investigaciones Cardiovasculares, CNIC, Madrid, Spain.

The positional information theory proposes that a coordinate system provides information to embryonic cells about their position and orientation along a patterning axis. Cells interpret this information to produce the appropriate pattern. During development, morphogens and interpreter transcription factors provide this information. Read More

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Transcription Factor-Based Fate Specification and Forward Programming for Neural Regeneration.

Front Cell Neurosci 2020 20;14:121. Epub 2020 May 20.

Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Faculty and University Hospital Bonn, Bonn, Germany.

Traditionally, generation of donor cells for brain repair has been dominated by the application of extrinsic growth factors and morphogens. Recent advances in cell engineering strategies such as reprogramming of somatic cells into induced pluripotent stem cells and direct cell fate conversion have impressively demonstrated the feasibility to manipulate cell identities by the overexpression of cell fate-determining transcription factors. These strategies are now increasingly implemented for transcription factor-guided differentiation of neural precursors and forward programming of pluripotent stem cells toward specific neural subtypes. Read More

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Molecular Regulation in Dopaminergic Neuron Development. Cues to Unveil Molecular Pathogenesis and Pharmacological Targets of Neurodegeneration.

Int J Mol Sci 2020 Jun 3;21(11). Epub 2020 Jun 3.

Institute of Genetics and Biophysics "Adriano Buzzati Traverso", CNR, 80131 Rome, Italy.

The relatively few dopaminergic neurons in the mammalian brain are mostly located in the midbrain and regulate many important neural functions, including motor integration, cognition, emotive behaviors and reward. Therefore, alteration of their function or degeneration leads to severe neurological and neuropsychiatric diseases. Unraveling the mechanisms of midbrain dopaminergic (mDA) phenotype induction and maturation and elucidating the role of the gene network involved in the development and maintenance of these neurons is of pivotal importance to rescue or substitute these cells in order to restore dopaminergic functions. Read More

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