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  • 1
    Publication Date: 2013-04-26
    Description: Skeletal muscle arises from the fusion of precursor myoblasts into multinucleated myofibres. Although conserved transcription factors and signalling proteins involved in myogenesis have been identified, upstream regulators are less well understood. Here we report an unexpected discovery that the membrane protein BAI1, previously linked to recognition of apoptotic cells by phagocytes, promotes myoblast fusion. Endogenous BAI1 expression increased during myoblast fusion, and BAI1 overexpression enhanced myoblast fusion by means of signalling through ELMO/Dock180/Rac1 proteins. During myoblast fusion, a fraction of myoblasts within the population underwent apoptosis and exposed phosphatidylserine, an established ligand for BAI1 (ref. 3). Blocking apoptosis potently impaired myoblast fusion, and adding back apoptotic myoblasts restored fusion. Furthermore, primary human myoblasts could be induced to form myotubes by adding apoptotic myoblasts, even under normal growth conditions. Mechanistically, apoptotic cells did not directly fuse with the healthy myoblasts, rather the apoptotic cells induced a contact-dependent signalling with neighbours to promote fusion among the healthy myoblasts. In vivo, myofibres from Bai1(-/-) mice are smaller than those from wild-type littermates. Muscle regeneration after injury was also impaired in Bai1(-/-)mice, highlighting a role for BAI1 in mammalian myogenesis. Collectively, these data identify apoptotic cells as a new type of cue that induces signalling via the phosphatidylserine receptor BAI1 to promote fusion of healthy myoblasts, with important implications for muscle development and repair.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773542/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773542/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hochreiter-Hufford, Amelia E -- Lee, Chang Sup -- Kinchen, Jason M -- Sokolowski, Jennifer D -- Arandjelovic, Sanja -- Call, Jarrod A -- Klibanov, Alexander L -- Yan, Zhen -- Mandell, James W -- Ravichandran, Kodi S -- P30 CA044579/CA/NCI NIH HHS/ -- R01 GM064709/GM/NIGMS NIH HHS/ -- T32 AI007496/AI/NIAID NIH HHS/ -- T32 AR007612/AR/NIAMS NIH HHS/ -- England -- Nature. 2013 May 9;497(7448):263-7. doi: 10.1038/nature12135. Epub 2013 Apr 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia 22908, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23615608" target="_blank"〉PubMed〈/a〉
    Keywords: Angiogenic Proteins/deficiency/genetics/*metabolism ; Animals ; Apoptosis/drug effects/*physiology ; Cell Communication ; Cell Differentiation ; *Cell Fusion ; Cell Line ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Muscle Development ; Muscle Fibers, Skeletal/cytology/metabolism/pathology ; Muscle, Skeletal/*cytology/metabolism ; Myoblasts/*cytology/metabolism ; Phosphatidylserines/metabolism ; Receptors, Cell Surface/deficiency/genetics/*metabolism ; *Signal Transduction
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-06-02
    Description: One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506234/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506234/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Louveau, Antoine -- Smirnov, Igor -- Keyes, Timothy J -- Eccles, Jacob D -- Rouhani, Sherin J -- Peske, J David -- Derecki, Noel C -- Castle, David -- Mandell, James W -- Lee, Kevin S -- Harris, Tajie H -- Kipnis, Jonathan -- P30 CA044579/CA/NCI NIH HHS/ -- R01 AG034113/AG/NIA NIH HHS/ -- R01 NS061973/NS/NINDS NIH HHS/ -- R01AG034113/AG/NIA NIH HHS/ -- R01NS061973/NS/NINDS NIH HHS/ -- England -- Nature. 2015 Jul 16;523(7560):337-41. doi: 10.1038/nature14432. Epub 2015 Jun 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA. ; 1] Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Beirne B. Carter Center for Immunology Research, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [3] Department of Medicine (Division of Allergy), School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA. ; 1] Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Beirne B. Carter Center for Immunology Research, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [3] Department of Microbiology, Immunology, and Cancer Biology, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA. ; Department of Cell Biology, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA. ; Department of Pathology (Neuropathology), School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA. ; 1] Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [3] Department of Neurosurgery, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA. ; 1] Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [3] Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26030524" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Central Nervous System/*anatomy & histology/cytology/*immunology ; Cranial Sinuses/anatomy & histology ; Female ; Humans ; Immune Tolerance/immunology ; Immunologic Surveillance/immunology ; Lymphatic Vessels/*anatomy & histology/cytology/*immunology ; Male ; Meninges/anatomy & histology/cytology/immunology ; Mice, Inbred C57BL ; T-Lymphocytes/cytology/immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2016-02-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Louveau, Antoine -- Smirnov, Igor -- Keyes, Timothy J -- Eccles, Jacob D -- Rouhani, Sherin J -- Peske, J David -- Derecki, Noel C -- Castle, David -- Mandell, James W -- Lee, Kevin S -- Harris, Tajie H -- Kipnis, Jonathan -- England -- Nature. 2016 Feb 24;533(7602):278. doi: 10.1038/nature16999.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26909581" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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