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HOXC9 regulates formation of parachordal lymphangioplasts and the thoracic duct in zebrafish via stabilin 2

HOXC9 belongs to the family of homeobox transcription factors, which are regulators of body patterning and development. HOXC9 acts as a negative regulator on blood endothelial cells but its function on lymphatic vessel development has not been studied. The hyaluronan receptor homologs stabilin 1 and...

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Published in:PloS one 2013-03, Vol.8 (3), p.e58311-e58311
Main Authors: Stoll, Sandra J, Bartsch, Susanne, Kroll, Jens
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description HOXC9 belongs to the family of homeobox transcription factors, which are regulators of body patterning and development. HOXC9 acts as a negative regulator on blood endothelial cells but its function on lymphatic vessel development has not been studied. The hyaluronan receptor homologs stabilin 1 and stabilin 2 are expressed in endothelial cells but their role in vascular development is poorly understood. This study was aimed at investigating the function of HOXC9, stabilin 2 and stabilin 1 in lymphatic vessel development in zebrafish and in endothelial cells. Morpholino-based expression silencing of HOXC9 repressed parachordal lymphangioblast assembly and thoracic duct formation in zebrafish. HOXC9 positively regulated stabilin 2 expression in zebrafish and in HUVECs and expression silencing of stabilin 2 phenocopied the HOXC9 morphant vascular phenotype. This effect could be compensated by HOXC9 mRNA injection in stabilin 2 morphant zebrafish embryos. Stabilin 1 also regulated parachordal lymphangioblast and thoracic duct formation in zebrafish but acts independently of HOXC9. On a cellular level stabilin 1 and stabilin 2 regulated endothelial cell migration and in-gel sprouting angiogenesis in endothelial cells. HOXC9 was identified as novel transcriptional regulator of parachordal lymphangioblast assembly and thoracic duct formation in zebrafish that acts via stabilin 2. Stabilin 1, which acts independently of HOXC9, has a similar function in zebrafish and both receptors control important cellular processes in endothelial cells.
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HOXC9 acts as a negative regulator on blood endothelial cells but its function on lymphatic vessel development has not been studied. The hyaluronan receptor homologs stabilin 1 and stabilin 2 are expressed in endothelial cells but their role in vascular development is poorly understood. This study was aimed at investigating the function of HOXC9, stabilin 2 and stabilin 1 in lymphatic vessel development in zebrafish and in endothelial cells. Morpholino-based expression silencing of HOXC9 repressed parachordal lymphangioblast assembly and thoracic duct formation in zebrafish. HOXC9 positively regulated stabilin 2 expression in zebrafish and in HUVECs and expression silencing of stabilin 2 phenocopied the HOXC9 morphant vascular phenotype. This effect could be compensated by HOXC9 mRNA injection in stabilin 2 morphant zebrafish embryos. Stabilin 1 also regulated parachordal lymphangioblast and thoracic duct formation in zebrafish but acts independently of HOXC9. On a cellular level stabilin 1 and stabilin 2 regulated endothelial cell migration and in-gel sprouting angiogenesis in endothelial cells. HOXC9 was identified as novel transcriptional regulator of parachordal lymphangioblast assembly and thoracic duct formation in zebrafish that acts via stabilin 2. Stabilin 1, which acts independently of HOXC9, has a similar function in zebrafish and both receptors control important cellular processes in endothelial cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23484014</pmid><doi>10.1371/journal.pone.0058311</doi><tpages>e58311</tpages><oa>free_for_read</oa></addata></record>
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1932-6203
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subjects Angiogenesis
Animals
Assembly
Biology
Blotting, Western
Cell adhesion & migration
Cell Adhesion Molecules, Neuronal - metabolism
Cell migration
Cytokines
Danio rerio
DNA Primers - genetics
Embryonic development
Embryos
Endothelial cells
Endothelial Cells - metabolism
Endothelium
Ethics
Gene Expression Regulation, Developmental - physiology
Genes
Green Fluorescent Proteins - metabolism
Homeobox
Homeodomain Proteins - metabolism
Homology
Human Umbilical Vein Endothelial Cells
Humans
Hyaluronic acid
Immunoglobulins
Lymphatic system
Lymphatic Vessels - embryology
Mathematics
Medical research
Medical technology
Medicine
Metastasis
Microscopy, Fluorescence
Morphogenesis
Pattern formation
Receptor mechanisms
Receptors
Receptors, Lymphocyte Homing - metabolism
Regulators
Reverse Transcriptase Polymerase Chain Reaction
RNA
Rodents
Studies
Thoracic duct
Thoracic Duct - embryology
Transcription factors
Transfection
Veins & arteries
Vertebrates
Zebrafish
Zebrafish - embryology
Zebrafish Proteins - metabolism
title HOXC9 regulates formation of parachordal lymphangioplasts and the thoracic duct in zebrafish via stabilin 2
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