23 results on '"Pitulescu, Mara E."'
Search Results
2. Control of cardiac jelly dynamics by NOTCH1 and NRG1 defines the building plan for trabeculation
- Author
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del Monte-Nieto, Gonzalo, Ramialison, Mirana, Adam, Arne A. S., Wu, Bingruo, Aharonov, Alla, D’Uva, Gabriele, Bourke, Lauren M., Pitulescu, Mara E., Chen, Hanying, de la Pompa, José Luis, Shou, Weinian, Adams, Ralf H., Harten, Sarah K., Tzahor, Eldad, Zhou, Bin, and Harvey, Richard P.
- Published
- 2018
- Full Text
- View/download PDF
3. Fine-Tuning of Sox17 and Canonical Wnt Coordinates the Permeability Properties of the Blood-Brain Barrier
- Author
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Corada, Monica, Orsenigo, Fabrizio, Bhat, Ganesh Parameshwar, Conze, Lei Liu, Breviario, Ferruccio, Cunha, Sara Isabel, Claesson-Welsh, Lena, Beznoussenko, Galina V., Mironov, Alexander A., Bacigaluppi, Marco, Martino, Gianvito, Pitulescu, Mara E., Adams, Ralf H., Magnusson, Peetra, and Dejana, Elisabetta
- Published
- 2019
- Full Text
- View/download PDF
4. Inducible gene targeting in the neonatal vasculature and analysis of retinal angiogenesis in mice
- Author
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Pitulescu, Mara E, Schmidt, Inga, Benedito, Rui, and Adams, Ralf H
- Published
- 2010
- Full Text
- View/download PDF
5. Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis
- Author
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Wang, Yingdi, Nakayama, Masanori, Pitulescu, Mara E., Schmidt, Tim S., Bochenek, Magdalena L., Sakakibara, Akira, Adams, Susanne, Davy, Alice, Deutsch, Urban, Lüthi, Urs, Barberis, Alcide, Benjamin, Laura E., Mäkinen, Taija, Nobes, Catherine D., and Adams, Ralf H.
- Published
- 2010
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- View/download PDF
6. Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis
- Author
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Sawamiphak, Suphansa, Seidel, Sascha, Essmann, Clara L., Wilkinson, George A., Pitulescu, Mara E., Acker, Till, and Acker-Palmer, Amparo
- Published
- 2010
- Full Text
- View/download PDF
7. Endothelial EphB4 maintains vascular integrity and transport function in adult heart.
- Author
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Luxán, Guillermo, Stewen, Jonas, Díaz, Noelia, Katsuhiro Kato, Maney, Sathish K., Aravamudhan, Anusha, Berkenfeld, Frank, Nagelmann, Nina, Drexler, Hannes C. A., Zeuschner, Dagmar, Faber, Cornelius, Schillers, Hermann, Hermann, Sven, Wiseman, John, Vaquerizas, Juan M., Pitulescu, Mara E., and Adams, Ralf H.
- Published
- 2019
- Full Text
- View/download PDF
8. Eph/ephrin molecules-a hub for signaling and endocytosis
- Author
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Pitulescu, Mara E. and Adams, Ralf H.
- Subjects
Cellular signal transduction -- Analysis ,Endocytosis -- Research ,Ephrins -- Chemical properties ,Ephrins -- Research ,Phosphotransferases -- Chemical properties ,Phosphotransferases -- Research ,Biological sciences - Published
- 2010
9. Ephrin-Bs Drive Junctional Downregulation and Actin Stress Fiber Disassembly to Enable Wound Re-epithelialization
- Author
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Nunan, Robert, Campbell, Jessica, Mori, Ryoichi, Pitulescu, Mara E., Jiang, Wen G., Harding, Keith G., Adams, Ralf H., Nobes, Catherine D., and Martin, Paul
- Subjects
lcsh:Biology (General) ,integumentary system ,lcsh:QH301-705.5 ,R1 - Abstract
For a skin wound to successfully heal, the cut epidermal-edge cells have to migrate forward at the interface between scab and healthy granulation tissue. Much is known about how lead-edge cells migrate, but very little is known about the mechanisms that enable active participation by cells further back. Here we show that ephrin-B1 and its receptor EphB2 are both upregulated in vivo, just for the duration of repair, in the first 70 or so rows of epidermal cells, and this signal leads to downregulation of the molecular components of adherens and tight (but not desmosomal) junctions, leading to loosening between neighbors and enabling shuffle room among epidermal cells. Additionally, this signaling leads to the shutdown of actomyosin stress fibers in these same epidermal cells, which may act to release tension within the wound monolayer. If this signaling axis is perturbed, then disrupted healing is a consequence in mouse and man. Epithelial migration is essential for skin wound healing., Cell Reports, 13(7), pp.1380-1395; 2015
- Published
- 2015
10. Polarized actin and VE-cadherin dynamics regulate junctional remodelling and cell migration during sprouting angiogenesis.
- Author
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Jiahui Cao, Ehling, Manuel, März, Sigrid, Seebach, Jochen, Tarbashevich, Katsiaryna, Sixta, Tomas, Pitulescu, Mara E., Werner, Ann-Cathrin, Flach, Boris, Montanez, Eloi, Raz, Erez, Adams, Ralf H., and Schnittler, Hans
- Subjects
NEOVASCULARIZATION ,ENDOTHELIAL cells ,CELL junctions ,CELL migration ,CADHERINS ,LAMELLIPODIA ,CELL motility ,MICROTUBULES - Abstract
VEGFR-2/Notch signalling regulates angiogenesis in part by driving the remodelling of endothelial cell junctions and by inducing cell migration. Here, we show that VEGF-induced polarized cell elongation increases cell perimeter and decreases the relative VE-cadherin concentration at junctions, triggering polarized formation of actin-driven junction-associated intermittent lamellipodia (JAIL) under control of the WASP/WAVE/ARP2/3 complex. JAIL allow formation of new VE-cadherin adhesion sites that are critical for cell migration and monolayer integrity. Whereas at the leading edge of the cell, large JAIL drive cell migration with supportive contraction, lateral junctions show small JAIL that allow relative cell movement. VEGFR-2 activation initiates cell elongation through dephosphorylation of junctional myosin light chain II, which leads to a local loss of tension to induce JAIL-mediated junctional remodelling. These events require both microtubules and polarized Rac activity. Together, we propose a model where polarized JAIL formation drives directed cell migration and junctional remodelling during sprouting angiogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
11. Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells.
- Author
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Ottone, Cristina, Krusche, Benjamin, Whitby, Ariadne, Clements, Melanie, Quadrato, Giorgia, Pitulescu, Mara E., Adams, Ralf H., and Parrinello, Simona
- Subjects
CELL communication ,NEURAL stem cells ,CELL differentiation ,BLOOD vessels ,PROGENITOR cells - Abstract
The vasculature is a prominent component of the subventricular zone neural stem cell niche. Although quiescent neural stem cells physically contact blood vessels at specialized endfeet, the significance of this interaction is not understood. In contrast, it is well established that vasculature-secreted soluble factors promote lineage progression of committed progenitors. Here we specifically investigated the role of cell-cell contact-dependent signalling in the vascular niche. Unexpectedly, we find that direct cell-cell interactions with endothelial cells enforce quiescence and promote stem cell identity. Mechanistically, endothelial ephrinB2 and Jagged1 mediate these effects by suppressing cell-cycle entry downstream of mitogens and inducing stemness genes to jointly inhibit differentiation. In vivo, endothelial-specific ablation of either of the genes which encode these proteins, Efnb2 and Jag1 respectively, aberrantly activates quiescent stem cells, resulting in depletion. Thus, we identify the vasculature as a critical niche compartment for stem cell maintenance, furthering our understanding of how anchorage to the niche maintains stem cells within a pro-differentiative microenvironment. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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- View/download PDF
12. Regulation of signaling interactions and receptor endocytosis in growing blood vessels.
- Author
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Pitulescu, Mara E and Adams, Ralf H
- Published
- 2014
- Full Text
- View/download PDF
13. Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis.
- Author
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Yingdi Wang, Nakayama, Masanori, Pitulescu, Mara E., Schmidt, Tim S., Bochenek, Magdalena L., Sakakibara, Akira, Adams, Susanne, Davy, Alice, Deutsch, Urban, Lüthi, Urs, Barberis, Alcide, Benjamin, Laura E., Mäkinen, Taija, Nobes, Catherine D., and Adams, Ralf H.
- Subjects
NEOVASCULARIZATION ,TISSUES ,VASCULAR diseases ,CELL proliferation ,VASCULAR endothelial growth factors ,LIGANDS (Biochemistry) ,PROTEIN-tyrosine kinases ,ENDOTHELIUM ,MITOGENS ,PROTEIN kinases - Abstract
In development, tissue regeneration or certain diseases, angiogenic growth leads to the expansion of blood vessels and the lymphatic vasculature. This involves endothelial cell proliferation as well as angiogenic sprouting, in which a subset of cells, termed tip cells, acquires motile, invasive behaviour and extends filopodial protrusions. Although it is already appreciated that angiogenesis is triggered by tissue-derived signals, such as vascular endothelial growth factor (VEGF) family growth factors, the resulting signalling processes in endothelial cells are only partly understood. Here we show with genetic experiments in mouse and zebrafish that ephrin-B2, a transmembrane ligand for Eph receptor tyrosine kinases, promotes sprouting behaviour and motility in the angiogenic endothelium. We link this pro-angiogenic function to a crucial role of ephrin-B2 in the VEGF signalling pathway, which we have studied in detail for VEGFR3, the receptor for VEGF-C. In the absence of ephrin-B2, the internalization of VEGFR3 in cultured cells and mutant mice is defective, which compromises downstream signal transduction by the small GTPase Rac1, Akt and the mitogen-activated protein kinase Erk. Our results show that full VEGFR3 signalling is coupled to receptor internalization. Ephrin-B2 is a key regulator of this process and thereby controls angiogenic and lymphangiogenic growth. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
14. TIPT2 and geminin interact with basal transcription factors to synergize in transcriptional regulation
- Author
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Pitulescu Mara E, Teichmann Martin, Luo Lingfei, and Kessel Michael
- Subjects
Transcriptional Activation ,Transcription, Genetic ,Chromosomal Proteins, Non-Histone ,Molecular Sequence Data ,lcsh:Animal biochemistry ,Cell Cycle Proteins ,macromolecular substances ,Biochemistry ,Cell Line ,lcsh:Biochemistry ,Mice ,Animals ,Humans ,lcsh:QD415-436 ,Amino Acid Sequence ,Promoter Regions, Genetic ,lcsh:QP501-801 ,Molecular Biology ,Cell Nucleus ,Geminin ,Nuclear Proteins ,TATA-Box Binding Protein ,Chromatin ,Protein Transport ,Gene Expression Regulation ,embryonic structures ,Research Article ,HeLa Cells ,Protein Binding ,Transcription Factors - Abstract
Background The re-replication inhibitor Geminin binds to several transcription factors including homeodomain proteins, and to members of the polycomb and the SWI/SNF complexes. Results Here we describe the TATA-binding protein-like factor-interacting protein (TIPT) isoform 2, as a strong binding partner of Geminin. TIPT2 is widely expressed in mouse embryonic and adult tissues, residing both in cyto- and nucleoplasma, and enriched in the nucleolus. Like Geminin, also TIPT2 interacts with several polycomb factors, with the general transcription factor TBP (TATA box binding protein), and with the related protein TBPL1 (TRF2). TIPT2 synergizes with geminin and TBP in the activation of TATA box-containing promoters, and with TBPL1 and geminin in the activation of the TATA-less NF1 promoter. Geminin and TIPT2 were detected in the chromatin near TBP/TBPL1 binding sites. Conclusion Together, our study introduces a novel transcriptional regulator and its function in cooperation with chromatin associated factors and the basal transcription machinery.
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15. Arteries are formed by vein-derived endothelial tip cells.
- Author
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Xu, Cong, Hasan, Sana S., Schmidt, Inga, Rocha, Susana F., Pitulescu, Mara E., Bussmann, Jeroen, Meyen, Dana, Raz, Erez, Adams, Ralf H., and Siekmann, Arndt F.
- Published
- 2014
- Full Text
- View/download PDF
16. Extracellular matrix dynamics reveals the building plan for cardiac trabeculation.
- Author
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del Monte-Nieto, Gonzalo, Ramialison, Mirana, Cherian, Anoop V., Wu, Bingruo, Aharonov, Alla, D’Uva, Gabriele, Bourke, Lauren M., Pitulescu, Mara E., Chen, Hanying, Shou, Weinian, Adams, Ralf H., Harten, Sarah K., Tzahor, Eldad, Zhou, Bin, Stainier, Didier Y., and Harvey, Richard P.
- Subjects
- *
EXTRACELLULAR matrix , *CARDIAC regeneration , *STEM cells , *HEART physiology , *VASCULAR endothelial growth factors , *PHYSIOLOGY - Published
- 2017
- Full Text
- View/download PDF
17. Induction of osteogenesis by bone-targeted Notch activation.
- Author
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Xu C, Dinh VV, Kruse K, Jeong HW, Watson EC, Adams S, Berkenfeld F, Stehling M, Rasouli SJ, Fan R, Chen R, Bedzhov I, Chen Q, Kato K, Pitulescu ME, and Adams RH
- Subjects
- Adaptor Proteins, Signal Transducing metabolism, Animals, Bone and Bones metabolism, Calcium-Binding Proteins metabolism, Chondrocytes metabolism, Endothelial Cells metabolism, Female, Human Umbilical Vein Endothelial Cells, Humans, Male, Mesenchymal Stem Cells metabolism, Mice, Mice, Inbred C57BL, Osteoblasts metabolism, Signal Transduction, Osteogenesis, Osteoporosis metabolism, Receptors, Notch metabolism
- Abstract
Declining bone mass is associated with aging and osteoporosis, a disease characterized by progressive weakening of the skeleton and increased fracture incidence. Growth and lifelong homeostasis of bone rely on interactions between different cell types including vascular cells and mesenchymal stromal cells (MSCs). As these interactions involve Notch signaling, we have explored whether treatment with secreted Notch ligand proteins can enhance osteogenesis in adult mice. We show that a bone-targeting, high affinity version of the ligand Delta-like 4, termed Dll4
(E12) , induces bone formation in male mice without causing adverse effects in other organs, which are known to rely on intact Notch signaling. Due to lower bone surface and thereby reduced retention of Dll4(E12) , the same approach failed to promote osteogenesis in female and ovariectomized mice but strongly enhanced trabecular bone formation in combination with parathyroid hormone. Single cell analysis of stromal cells indicates that Dll4(E12) primarily acts on MSCs and has comparably minor effects on osteoblasts, endothelial cells, or chondrocytes. We propose that activation of Notch signaling by bone-targeted fusion proteins might be therapeutically useful and can avoid detrimental effects in Notch-dependent processes in other organs., Competing Interests: CX, VD, KK, HJ, EW, SA, FB, MS, SR, RF, RC, IB, QC, KK, MP, RA No competing interests declared, (© 2022, Xu et al.)- Published
- 2022
- Full Text
- View/download PDF
18. Polarized actin and VE-cadherin dynamics regulate junctional remodelling and cell migration during sprouting angiogenesis.
- Author
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Cao J, Ehling M, März S, Seebach J, Tarbashevich K, Sixta T, Pitulescu ME, Werner AC, Flach B, Montanez E, Raz E, Adams RH, and Schnittler H
- Subjects
- Actin-Related Protein 2 metabolism, Actin-Related Protein 2-3 Complex metabolism, Actin-Related Protein 3 metabolism, Actins drug effects, Antigens, CD drug effects, Cadherins drug effects, Cardiac Myosins metabolism, Cell Adhesion, Cell Movement drug effects, Cell Polarity drug effects, Endothelial Cells drug effects, Endothelial Cells physiology, Endothelium, Vascular, Human Umbilical Vein Endothelial Cells, Humans, Intercellular Junctions drug effects, Microtubules drug effects, Microtubules metabolism, Models, Cardiovascular, Myosin Light Chains metabolism, Neovascularization, Physiologic drug effects, Pseudopodia drug effects, Pseudopodia metabolism, Pseudopodia physiology, Signal Transduction, Vascular Endothelial Growth Factor A pharmacology, Vascular Endothelial Growth Factor Receptor-2 metabolism, Vascular Remodeling, Wiskott-Aldrich Syndrome Protein metabolism, Wiskott-Aldrich Syndrome Protein Family metabolism, rac GTP-Binding Proteins metabolism, Actins metabolism, Antigens, CD metabolism, Cadherins metabolism, Cell Movement physiology, Cell Polarity physiology, Endothelial Cells metabolism, Intercellular Junctions metabolism, Neovascularization, Physiologic physiology, Vascular Endothelial Growth Factor A metabolism
- Abstract
VEGFR-2/Notch signalling regulates angiogenesis in part by driving the remodelling of endothelial cell junctions and by inducing cell migration. Here, we show that VEGF-induced polarized cell elongation increases cell perimeter and decreases the relative VE-cadherin concentration at junctions, triggering polarized formation of actin-driven junction-associated intermittent lamellipodia (JAIL) under control of the WASP/WAVE/ARP2/3 complex. JAIL allow formation of new VE-cadherin adhesion sites that are critical for cell migration and monolayer integrity. Whereas at the leading edge of the cell, large JAIL drive cell migration with supportive contraction, lateral junctions show small JAIL that allow relative cell movement. VEGFR-2 activation initiates cell elongation through dephosphorylation of junctional myosin light chain II, which leads to a local loss of tension to induce JAIL-mediated junctional remodelling. These events require both microtubules and polarized Rac activity. Together, we propose a model where polarized JAIL formation drives directed cell migration and junctional remodelling during sprouting angiogenesis.
- Published
- 2017
- Full Text
- View/download PDF
19. Dll4 and Notch signalling couples sprouting angiogenesis and artery formation.
- Author
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Pitulescu ME, Schmidt I, Giaimo BD, Antoine T, Berkenfeld F, Ferrante F, Park H, Ehling M, Biljes D, Rocha SF, Langen UH, Stehling M, Nagasawa T, Ferrara N, Borggrefe T, and Adams RH
- Subjects
- Adaptor Proteins, Signal Transducing, Animals, Calcium-Binding Proteins, Cell Communication, Cell Differentiation, Cell Lineage, Cell Movement, Cell Proliferation, Cells, Cultured, Female, Gene Expression Regulation, Genotype, Intracellular Signaling Peptides and Proteins genetics, Jagged-1 Protein genetics, Jagged-1 Protein metabolism, Male, Membrane Proteins genetics, Mice, Inbred C57BL, Mice, Transgenic, Phenotype, Receptor, Notch1 genetics, Receptors, CXCR4 genetics, Receptors, CXCR4 metabolism, Retinal Artery cytology, Signal Transduction, Time Factors, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor A metabolism, Endothelial Cells metabolism, Intracellular Signaling Peptides and Proteins metabolism, Membrane Proteins metabolism, Neovascularization, Physiologic, Receptor, Notch1 metabolism, Retinal Artery metabolism
- Abstract
Endothelial sprouting and proliferation are tightly coordinated processes mediating the formation of new blood vessels during physiological and pathological angiogenesis. Endothelial tip cells lead sprouts and are thought to suppress tip-like behaviour in adjacent stalk endothelial cells by activating Notch. Here, we show with genetic experiments in postnatal mice that the level of active Notch signalling is more important than the direct Dll4-mediated cell-cell communication between endothelial cells. We identify endothelial expression of VEGF-A and of the chemokine receptor CXCR4 as key processes controlling Notch-dependent vessel growth. Surprisingly, genetic experiments targeting endothelial tip cells in vivo reveal that they retain their function without Dll4 and are also not replaced by adjacent, Dll4-positive cells. Instead, activation of Notch directs tip-derived endothelial cells into developing arteries and thereby establishes that Dll4-Notch signalling couples sprouting angiogenesis and artery formation.
- Published
- 2017
- Full Text
- View/download PDF
20. Cell-matrix signals specify bone endothelial cells during developmental osteogenesis.
- Author
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Langen UH, Pitulescu ME, Kim JM, Enriquez-Gasca R, Sivaraj KK, Kusumbe AP, Singh A, Di Russo J, Bixel MG, Zhou B, Sorokin L, Vaquerizas JM, and Adams RH
- Subjects
- Adipokines metabolism, Animals, Apelin, Bone and Bones blood supply, Bone and Bones diagnostic imaging, Capillaries cytology, Cell Adhesion, Flow Cytometry, Immunohistochemistry, Integrases metabolism, Integrin beta1 metabolism, Intercellular Signaling Peptides and Proteins metabolism, Mice, Inbred C57BL, Mice, Mutant Strains, Neovascularization, Physiologic, Phenotype, X-Ray Microtomography, Bone and Bones cytology, Endothelial Cells metabolism, Extracellular Matrix metabolism, Osteogenesis, Signal Transduction
- Abstract
Blood vessels in the mammalian skeletal system control bone formation and support haematopoiesis by generating local niche environments. While a specialized capillary subtype, termed type H, has been recently shown to couple angiogenesis and osteogenesis in adolescent, adult and ageing mice, little is known about the formation of specific endothelial cell populations during early developmental endochondral bone formation. Here, we report that embryonic and early postnatal long bone contains a specialized endothelial cell subtype, termed type E, which strongly supports osteoblast lineage cells and later gives rise to other endothelial cell subpopulations. The differentiation and functional properties of bone endothelial cells require cell-matrix signalling interactions. Loss of endothelial integrin β1 leads to endothelial cell differentiation defects and impaired postnatal bone growth, which is, in part, phenocopied by endothelial cell-specific laminin α5 mutants. Our work outlines fundamental principles of vessel formation and endothelial cell differentiation in the developing skeletal system.
- Published
- 2017
- Full Text
- View/download PDF
21. Ephrin-Bs Drive Junctional Downregulation and Actin Stress Fiber Disassembly to Enable Wound Re-epithelialization.
- Author
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Nunan R, Campbell J, Mori R, Pitulescu ME, Jiang WG, Harding KG, Adams RH, Nobes CD, and Martin P
- Subjects
- Animals, Cell Line, Down-Regulation, Humans, Male, Mice, Inbred C57BL, Mice, Knockout, Protein Multimerization, Receptors, Eph Family metabolism, Signal Transduction, Ephrin-B1 physiology, Ephrin-B2 physiology, Epithelial Cells physiology, Re-Epithelialization, Stress Fibers metabolism
- Abstract
For a skin wound to successfully heal, the cut epidermal-edge cells have to migrate forward at the interface between scab and healthy granulation tissue. Much is known about how lead-edge cells migrate, but very little is known about the mechanisms that enable active participation by cells further back. Here we show that ephrin-B1 and its receptor EphB2 are both upregulated in vivo, just for the duration of repair, in the first 70 or so rows of epidermal cells, and this signal leads to downregulation of the molecular components of adherens and tight (but not desmosomal) junctions, leading to loosening between neighbors and enabling shuffle room among epidermal cells. Additionally, this signaling leads to the shutdown of actomyosin stress fibers in these same epidermal cells, which may act to release tension within the wound monolayer. If this signaling axis is perturbed, then disrupted healing is a consequence in mouse and man., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
22. TIPT2 and geminin interact with basal transcription factors to synergize in transcriptional regulation.
- Author
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Pitulescu ME, Teichmann M, Luo L, and Kessel M
- Subjects
- Amino Acid Sequence, Animals, Cell Cycle Proteins chemistry, Cell Cycle Proteins genetics, Cell Line, Cell Nucleus genetics, Cell Nucleus metabolism, Chromatin metabolism, Chromosomal Proteins, Non-Histone chemistry, Chromosomal Proteins, Non-Histone genetics, Geminin, HeLa Cells, Humans, Mice, Molecular Sequence Data, Nuclear Proteins chemistry, Nuclear Proteins genetics, Promoter Regions, Genetic, Protein Binding, Protein Transport, TATA-Box Binding Protein genetics, TATA-Box Binding Protein metabolism, Transcription Factors chemistry, Transcription Factors genetics, Transcriptional Activation, Cell Cycle Proteins metabolism, Chromosomal Proteins, Non-Histone metabolism, Gene Expression Regulation, Nuclear Proteins metabolism, Transcription Factors metabolism, Transcription, Genetic
- Abstract
Background: The re-replication inhibitor Geminin binds to several transcription factors including homeodomain proteins, and to members of the polycomb and the SWI/SNF complexes., Results: Here we describe the TATA-binding protein-like factor-interacting protein (TIPT) isoform 2, as a strong binding partner of Geminin. TIPT2 is widely expressed in mouse embryonic and adult tissues, residing both in cyto- and nucleoplasma, and enriched in the nucleolus. Like Geminin, also TIPT2 interacts with several polycomb factors, with the general transcription factor TBP (TATA box binding protein), and with the related protein TBPL1 (TRF2). TIPT2 synergizes with geminin and TBP in the activation of TATA box-containing promoters, and with TBPL1 and geminin in the activation of the TATA-less NF1 promoter. Geminin and TIPT2 were detected in the chromatin near TBP/TBPL1 binding sites., Conclusion: Together, our study introduces a novel transcriptional regulator and its function in cooperation with chromatin associated factors and the basal transcription machinery.
- Published
- 2009
- Full Text
- View/download PDF
23. MicroRNAs in organogenesis and disease.
- Author
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Asli NS, Pitulescu ME, and Kessel M
- Subjects
- Animals, Cell Cycle genetics, Central Nervous System embryology, Heart embryology, Heart Diseases genetics, Hematopoiesis genetics, Humans, Liver embryology, MicroRNAs physiology, Models, Genetic, Muscles embryology, Muscular Diseases genetics, Neoplasms genetics, Organogenesis physiology, Pancreas embryology, Disease genetics, MicroRNAs genetics, Organogenesis genetics
- Abstract
Large numbers and quantities of different, small RNA molecules are present in the cytoplasm of animal and plant cells. One subclass of these molecules is represented by the noncoding microRNAs. Since their discovery in the 1990s a multitude of basic information has accumulated, which has identified their function in post-transcriptional control, either via degradation or translational inhibition of target mRNAs. This function is in most of the cases a finetuning of gene expression, working in parallel with transcriptional regulatory processes. MicroRNA expression profiles are highly dynamic during embryonic development and in adulthood. Misexpression of microRNAs can perturb embryogenesis, organogenesis, tissue homeostasis and the cell cycle. Evidence from gain- and loss-of function studies indicates roles for microRNAs in pathophysiologic states including cardiac hypertrophy, muscle dystrophy, hepatitis infection, diabetes, Parkinson syndrome, hematological malignancies and other types of cancer. In this review, we focus on studies addressing the role of various microRNAs in heart, muscle, liver, pancreas, central nervous system, and hematopoiesis.
- Published
- 2008
- Full Text
- View/download PDF
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