ingest cdrApp 2017-08-15T22:05:41.246Z d91e81c8-5a8a-4e8a-976c-cad4e396e5ee modifyDatastreamByValue RELS-EXT fedoraAdmin 2017-08-15T22:06:31.945Z Setting exclusive relation modifyDatastreamByValue RELS-EXT fedoraAdmin 2017-08-15T22:06:40.950Z Setting exclusive relation addDatastream MD_TECHNICAL fedoraAdmin 2017-08-15T22:06:49.965Z Adding technical metadata derived by FITS modifyDatastreamByValue RELS-EXT fedoraAdmin 2017-08-15T22:07:07.860Z Setting exclusive relation addDatastream MD_FULL_TEXT fedoraAdmin 2017-08-15T22:07:08.832Z Adding full text metadata extracted by Apache Tika modifyDatastreamByValue RELS-EXT fedoraAdmin 2017-08-15T22:07:09.688Z Setting exclusive relation modifyDatastreamByValue RELS-EXT cdrApp 2017-08-22T13:58:41.799Z Setting exclusive relation modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-01-25T13:27:31.733Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-01-27T13:25:34.845Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-03-14T10:39:01.190Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-05-18T13:31:04.214Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-11T09:12:19.030Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-18T05:17:17.492Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-16T18:24:56.475Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-27T14:12:07.329Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-10-12T05:23:19.121Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-03-21T15:13:10.095Z Diana Chong Author Curriculum in Genetics and Molecular Biology School of Medicine SPROUTING ANGIOGENESIS DURING RETINAL DEVELOPMENT AND WOUND HEALING Endothelial cells, the cells that line blood vessels, become activated during development to sprout and form new vessels in a process termed angiogenesis. During development, sprouting angiogenesis is robust and is the main driving force behind vascularization of new tissues in the embryo. In contrast, endothelial cells are mainly quiescent in the adult and only become reactivated during physiological or pathological angiogenesis. The bone morphogenetic protein (BMP) pathway has been shown to be a pro-angiogenic cue. During postnatal retinal development, BMP receptors are expressed in the retinal vasculature and BMP ligands are expressed throughout the retina. Here, we show that deletion of BMP receptors, Alk1, Alk2, Alk3, and BMPR2 affect sprouting angiogenesis during development. Endothelial specific deletion of Alk2, Alk3, and BMPR2 resulted in decreased sprouting at the vascular front as well as branching in the vascular plexus, whereas deletion of Alk1 resulted in increased sprouting. These data point to a requirement of BMP signaling for proper patterning of the retinal vasculature during development. We also analyzed tortuous microvessels, abnormal vessels that arise during the wound healing process. Tortuous vessels are observed in many diseases, most notably cancer and diabetes. However, the causes and consequences of these abnormal vessels have not been elucidated. Here, we use intravital, high-resolution imaging to examine the formation, resolution, and sprouting of tortuous microvessels during wound healing. We found that tortuous microvessels are mainly located 100-300 μm from the wound center and that tortuous microvessels resolved by becoming normal again. Additionally, using fluorescent, microcarrier beads we found that beads became stuck in tortuous microvessels suggesting differences in flow. The shapes of endothelial cells within tortuous microvessels are round, indicative of activated cells, and exhibit sprout initiations at a higher frequency than normal vessels. Thus, we highlight an important, undiscovered feature of tortuous microvessels, sprouting, that can be used as a therapeutic target to normalize tortuous vessels during disease. Summer 2017 2017 Molecular biology Biology Genetics angiogenesis, BMP, intravital, tortuous microvessels, wound healing eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Genetics and Molecular Biology Victoria Bautch Thesis advisor Kathleen Caron Thesis advisor Frank Conlon Thesis advisor John Rawls Thesis advisor Paul Dayton Thesis advisor text Diana Chong Creator Curriculum in Genetics and Molecular Biology School of Medicine SPROUTING ANGIOGENESIS DURING RETINAL DEVELOPMENT AND WOUND HEALING Endothelial cells, the cells that line blood vessels, become activated during development to sprout and form new vessels in a process termed angiogenesis. During development, sprouting angiogenesis is robust and is the main driving force behind vascularization of new tissues in the embryo. In contrast, endothelial cells are mainly quiescent in the adult and only become reactivated during physiological or pathological angiogenesis. The bone morphogenetic protein (BMP) pathway has been shown to be a pro-angiogenic cue. During postnatal retinal development, BMP receptors are expressed in the retinal vasculature and BMP ligands are expressed throughout the retina. Here, we show that deletion of BMP receptors, Alk1, Alk2, Alk3, and BMPR2 affect sprouting angiogenesis during development. Endothelial specific deletion of Alk2, Alk3, and BMPR2 resulted in decreased sprouting at the vascular front as well as branching in the vascular plexus, whereas deletion of Alk1 resulted in increased sprouting. These data point to a requirement of BMP signaling for proper patterning of the retinal vasculature during development. We also analyzed tortuous microvessels, abnormal vessels that arise during the wound healing process. Tortuous vessels are observed in many diseases, most notably cancer and diabetes. However, the causes and consequences of these abnormal vessels have not been elucidated. Here, we use intravital, high-resolution imaging to examine the formation, resolution, and sprouting of tortuous microvessels during wound healing. We found that tortuous microvessels are mainly located 100-300 μm from the wound center and that tortuous microvessels resolved by becoming normal again. Additionally, using fluorescent, microcarrier beads we found that beads became stuck in tortuous microvessels suggesting differences in flow. The shapes of endothelial cells within tortuous microvessels are round, indicative of activated cells, and exhibit sprout initiations at a higher frequency than normal vessels. Thus, we highlight an important, undiscovered feature of tortuous microvessels, sprouting, that can be used as a therapeutic target to normalize tortuous vessels during disease. Summer 2017 2017 Molecular biology Biology Genetics angiogenesis, BMP, intravital, tortuous microvessels, wound healing eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Genetics and Molecular Biology Victoria Bautch Thesis advisor Kathleen Caron Thesis advisor Frank Conlon Thesis advisor John Rawls Thesis advisor Paul Dayton Thesis advisor text Diana Chong Creator Curriculum in Genetics and Molecular Biology School of Medicine SPROUTING ANGIOGENESIS DURING RETINAL DEVELOPMENT AND WOUND HEALING Endothelial cells, the cells that line blood vessels, become activated during development to sprout and form new vessels in a process termed angiogenesis. During development, sprouting angiogenesis is robust and is the main driving force behind vascularization of new tissues in the embryo. In contrast, endothelial cells are mainly quiescent in the adult and only become reactivated during physiological or pathological angiogenesis. The bone morphogenetic protein (BMP) pathway has been shown to be a pro-angiogenic cue. During postnatal retinal development, BMP receptors are expressed in the retinal vasculature and BMP ligands are expressed throughout the retina. Here, we show that deletion of BMP receptors, Alk1, Alk2, Alk3, and BMPR2 affect sprouting angiogenesis during development. Endothelial specific deletion of Alk2, Alk3, and BMPR2 resulted in decreased sprouting at the vascular front as well as branching in the vascular plexus, whereas deletion of Alk1 resulted in increased sprouting. These data point to a requirement of BMP signaling for proper patterning of the retinal vasculature during development. We also analyzed tortuous microvessels, abnormal vessels that arise during the wound healing process. Tortuous vessels are observed in many diseases, most notably cancer and diabetes. However, the causes and consequences of these abnormal vessels have not been elucidated. Here, we use intravital, high-resolution imaging to examine the formation, resolution, and sprouting of tortuous microvessels during wound healing. We found that tortuous microvessels are mainly located 100-300 μm from the wound center and that tortuous microvessels resolved by becoming normal again. Additionally, using fluorescent, microcarrier beads we found that beads became stuck in tortuous microvessels suggesting differences in flow. The shapes of endothelial cells within tortuous microvessels are round, indicative of activated cells, and exhibit sprout initiations at a higher frequency than normal vessels. Thus, we highlight an important, undiscovered feature of tortuous microvessels, sprouting, that can be used as a therapeutic target to normalize tortuous vessels during disease. Summer 2017 2017 Molecular biology Biology Genetics angiogenesis, BMP, intravital, tortuous microvessels, wound healing eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Genetics and Molecular Biology Victoria Bautch Thesis advisor Kathleen Caron Thesis advisor Frank Conlon Thesis advisor John Rawls Thesis advisor Paul Dayton Thesis advisor text Diana Chong Creator Curriculum in Genetics and Molecular Biology School of Medicine SPROUTING ANGIOGENESIS DURING RETINAL DEVELOPMENT AND WOUND HEALING Endothelial cells, the cells that line blood vessels, become activated during development to sprout and form new vessels in a process termed angiogenesis. During development, sprouting angiogenesis is robust and is the main driving force behind vascularization of new tissues in the embryo. In contrast, endothelial cells are mainly quiescent in the adult and only become reactivated during physiological or pathological angiogenesis. The bone morphogenetic protein (BMP) pathway has been shown to be a pro-angiogenic cue. During postnatal retinal development, BMP receptors are expressed in the retinal vasculature and BMP ligands are expressed throughout the retina. Here, we show that deletion of BMP receptors, Alk1, Alk2, Alk3, and BMPR2 affect sprouting angiogenesis during development. Endothelial specific deletion of Alk2, Alk3, and BMPR2 resulted in decreased sprouting at the vascular front as well as branching in the vascular plexus, whereas deletion of Alk1 resulted in increased sprouting. These data point to a requirement of BMP signaling for proper patterning of the retinal vasculature during development. We also analyzed tortuous microvessels, abnormal vessels that arise during the wound healing process. Tortuous vessels are observed in many diseases, most notably cancer and diabetes. However, the causes and consequences of these abnormal vessels have not been elucidated. Here, we use intravital, high-resolution imaging to examine the formation, resolution, and sprouting of tortuous microvessels during wound healing. We found that tortuous microvessels are mainly located 100-300 μm from the wound center and that tortuous microvessels resolved by becoming normal again. Additionally, using fluorescent, microcarrier beads we found that beads became stuck in tortuous microvessels suggesting differences in flow. The shapes of endothelial cells within tortuous microvessels are round, indicative of activated cells, and exhibit sprout initiations at a higher frequency than normal vessels. Thus, we highlight an important, undiscovered feature of tortuous microvessels, sprouting, that can be used as a therapeutic target to normalize tortuous vessels during disease. 2017-08 2017 Molecular biology Biology Genetics angiogenesis, BMP, intravital, tortuous microvessels, wound healing eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Genetics and Molecular Biology Victoria Bautch Thesis advisor Kathleen Caron Thesis advisor Frank Conlon Thesis advisor John Rawls Thesis advisor Paul Dayton Thesis advisor text Diana Chong Creator Curriculum in Genetics and Molecular Biology School of Medicine SPROUTING ANGIOGENESIS DURING RETINAL DEVELOPMENT AND WOUND HEALING Endothelial cells, the cells that line blood vessels, become activated during development to sprout and form new vessels in a process termed angiogenesis. During development, sprouting angiogenesis is robust and is the main driving force behind vascularization of new tissues in the embryo. In contrast, endothelial cells are mainly quiescent in the adult and only become reactivated during physiological or pathological angiogenesis. The bone morphogenetic protein (BMP) pathway has been shown to be a pro-angiogenic cue. During postnatal retinal development, BMP receptors are expressed in the retinal vasculature and BMP ligands are expressed throughout the retina. Here, we show that deletion of BMP receptors, Alk1, Alk2, Alk3, and BMPR2 affect sprouting angiogenesis during development. Endothelial specific deletion of Alk2, Alk3, and BMPR2 resulted in decreased sprouting at the vascular front as well as branching in the vascular plexus, whereas deletion of Alk1 resulted in increased sprouting. These data point to a requirement of BMP signaling for proper patterning of the retinal vasculature during development. We also analyzed tortuous microvessels, abnormal vessels that arise during the wound healing process. Tortuous vessels are observed in many diseases, most notably cancer and diabetes. However, the causes and consequences of these abnormal vessels have not been elucidated. Here, we use intravital, high-resolution imaging to examine the formation, resolution, and sprouting of tortuous microvessels during wound healing. We found that tortuous microvessels are mainly located 100-300 μm from the wound center and that tortuous microvessels resolved by becoming normal again. Additionally, using fluorescent, microcarrier beads we found that beads became stuck in tortuous microvessels suggesting differences in flow. The shapes of endothelial cells within tortuous microvessels are round, indicative of activated cells, and exhibit sprout initiations at a higher frequency than normal vessels. Thus, we highlight an important, undiscovered feature of tortuous microvessels, sprouting, that can be used as a therapeutic target to normalize tortuous vessels during disease. 2017 Molecular biology Biology Genetics angiogenesis, BMP, intravital, tortuous microvessels, wound healing eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Genetics and Molecular Biology Victoria Bautch Thesis advisor Kathleen Caron Thesis advisor Frank Conlon Thesis advisor John Rawls Thesis advisor Paul Dayton Thesis advisor text 2017-08 Diana Chong Creator Curriculum in Genetics and Molecular Biology School of Medicine SPROUTING ANGIOGENESIS DURING RETINAL DEVELOPMENT AND WOUND HEALING Endothelial cells, the cells that line blood vessels, become activated during development to sprout and form new vessels in a process termed angiogenesis. During development, sprouting angiogenesis is robust and is the main driving force behind vascularization of new tissues in the embryo. In contrast, endothelial cells are mainly quiescent in the adult and only become reactivated during physiological or pathological angiogenesis. The bone morphogenetic protein (BMP) pathway has been shown to be a pro-angiogenic cue. During postnatal retinal development, BMP receptors are expressed in the retinal vasculature and BMP ligands are expressed throughout the retina. Here, we show that deletion of BMP receptors, Alk1, Alk2, Alk3, and BMPR2 affect sprouting angiogenesis during development. Endothelial specific deletion of Alk2, Alk3, and BMPR2 resulted in decreased sprouting at the vascular front as well as branching in the vascular plexus, whereas deletion of Alk1 resulted in increased sprouting. These data point to a requirement of BMP signaling for proper patterning of the retinal vasculature during development. We also analyzed tortuous microvessels, abnormal vessels that arise during the wound healing process. Tortuous vessels are observed in many diseases, most notably cancer and diabetes. However, the causes and consequences of these abnormal vessels have not been elucidated. Here, we use intravital, high-resolution imaging to examine the formation, resolution, and sprouting of tortuous microvessels during wound healing. We found that tortuous microvessels are mainly located 100-300 μm from the wound center and that tortuous microvessels resolved by becoming normal again. Additionally, using fluorescent, microcarrier beads we found that beads became stuck in tortuous microvessels suggesting differences in flow. The shapes of endothelial cells within tortuous microvessels are round, indicative of activated cells, and exhibit sprout initiations at a higher frequency than normal vessels. Thus, we highlight an important, undiscovered feature of tortuous microvessels, sprouting, that can be used as a therapeutic target to normalize tortuous vessels during disease. 2017 Molecular biology Biology Genetics angiogenesis, BMP, intravital, tortuous microvessels, wound healing eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Genetics and Molecular Biology Victoria Bautch Thesis advisor Kathleen Caron Thesis advisor Frank Conlon Thesis advisor John Rawls Thesis advisor Paul Dayton Thesis advisor text 2017-08 Diana Chong Creator Curriculum in Genetics and Molecular Biology School of Medicine SPROUTING ANGIOGENESIS DURING RETINAL DEVELOPMENT AND WOUND HEALING Endothelial cells, the cells that line blood vessels, become activated during development to sprout and form new vessels in a process termed angiogenesis. During development, sprouting angiogenesis is robust and is the main driving force behind vascularization of new tissues in the embryo. In contrast, endothelial cells are mainly quiescent in the adult and only become reactivated during physiological or pathological angiogenesis. The bone morphogenetic protein (BMP) pathway has been shown to be a pro-angiogenic cue. During postnatal retinal development, BMP receptors are expressed in the retinal vasculature and BMP ligands are expressed throughout the retina. Here, we show that deletion of BMP receptors, Alk1, Alk2, Alk3, and BMPR2 affect sprouting angiogenesis during development. Endothelial specific deletion of Alk2, Alk3, and BMPR2 resulted in decreased sprouting at the vascular front as well as branching in the vascular plexus, whereas deletion of Alk1 resulted in increased sprouting. These data point to a requirement of BMP signaling for proper patterning of the retinal vasculature during development. We also analyzed tortuous microvessels, abnormal vessels that arise during the wound healing process. Tortuous vessels are observed in many diseases, most notably cancer and diabetes. However, the causes and consequences of these abnormal vessels have not been elucidated. Here, we use intravital, high-resolution imaging to examine the formation, resolution, and sprouting of tortuous microvessels during wound healing. We found that tortuous microvessels are mainly located 100-300 μm from the wound center and that tortuous microvessels resolved by becoming normal again. Additionally, using fluorescent, microcarrier beads we found that beads became stuck in tortuous microvessels suggesting differences in flow. The shapes of endothelial cells within tortuous microvessels are round, indicative of activated cells, and exhibit sprout initiations at a higher frequency than normal vessels. Thus, we highlight an important, undiscovered feature of tortuous microvessels, sprouting, that can be used as a therapeutic target to normalize tortuous vessels during disease. 2017 Molecular biology Biology Genetics angiogenesis, BMP, intravital, tortuous microvessels, wound healing eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Genetics and Molecular Biology Victoria Bautch Thesis advisor Kathleen Caron Thesis advisor Frank Conlon Thesis advisor John Rawls Thesis advisor Paul Dayton Thesis advisor text 2017-08 Diana Chong Creator Curriculum in Genetics and Molecular Biology School of Medicine SPROUTING ANGIOGENESIS DURING RETINAL DEVELOPMENT AND WOUND HEALING Endothelial cells, the cells that line blood vessels, become activated during development to sprout and form new vessels in a process termed angiogenesis. During development, sprouting angiogenesis is robust and is the main driving force behind vascularization of new tissues in the embryo. In contrast, endothelial cells are mainly quiescent in the adult and only become reactivated during physiological or pathological angiogenesis. The bone morphogenetic protein (BMP) pathway has been shown to be a pro-angiogenic cue. During postnatal retinal development, BMP receptors are expressed in the retinal vasculature and BMP ligands are expressed throughout the retina. Here, we show that deletion of BMP receptors, Alk1, Alk2, Alk3, and BMPR2 affect sprouting angiogenesis during development. Endothelial specific deletion of Alk2, Alk3, and BMPR2 resulted in decreased sprouting at the vascular front as well as branching in the vascular plexus, whereas deletion of Alk1 resulted in increased sprouting. These data point to a requirement of BMP signaling for proper patterning of the retinal vasculature during development. We also analyzed tortuous microvessels, abnormal vessels that arise during the wound healing process. Tortuous vessels are observed in many diseases, most notably cancer and diabetes. However, the causes and consequences of these abnormal vessels have not been elucidated. Here, we use intravital, high-resolution imaging to examine the formation, resolution, and sprouting of tortuous microvessels during wound healing. We found that tortuous microvessels are mainly located 100-300 μm from the wound center and that tortuous microvessels resolved by becoming normal again. Additionally, using fluorescent, microcarrier beads we found that beads became stuck in tortuous microvessels suggesting differences in flow. The shapes of endothelial cells within tortuous microvessels are round, indicative of activated cells, and exhibit sprout initiations at a higher frequency than normal vessels. Thus, we highlight an important, undiscovered feature of tortuous microvessels, sprouting, that can be used as a therapeutic target to normalize tortuous vessels during disease. 2017 Molecular biology Biology Genetics angiogenesis, BMP, intravital, tortuous microvessels, wound healing eng Doctor of Philosophy Dissertation Genetics and Molecular Biology Victoria Bautch Thesis advisor Kathleen Caron Thesis advisor Frank Conlon Thesis advisor John Rawls Thesis advisor Paul Dayton Thesis advisor text 2017-08 University of North Carolina at Chapel Hill Degree granting institution Diana Chong Creator Curriculum in Genetics and Molecular Biology School of Medicine SPROUTING ANGIOGENESIS DURING RETINAL DEVELOPMENT AND WOUND HEALING Endothelial cells, the cells that line blood vessels, become activated during development to sprout and form new vessels in a process termed angiogenesis. During development, sprouting angiogenesis is robust and is the main driving force behind vascularization of new tissues in the embryo. In contrast, endothelial cells are mainly quiescent in the adult and only become reactivated during physiological or pathological angiogenesis. The bone morphogenetic protein (BMP) pathway has been shown to be a pro-angiogenic cue. During postnatal retinal development, BMP receptors are expressed in the retinal vasculature and BMP ligands are expressed throughout the retina. Here, we show that deletion of BMP receptors, Alk1, Alk2, Alk3, and BMPR2 affect sprouting angiogenesis during development. Endothelial specific deletion of Alk2, Alk3, and BMPR2 resulted in decreased sprouting at the vascular front as well as branching in the vascular plexus, whereas deletion of Alk1 resulted in increased sprouting. These data point to a requirement of BMP signaling for proper patterning of the retinal vasculature during development. We also analyzed tortuous microvessels, abnormal vessels that arise during the wound healing process. Tortuous vessels are observed in many diseases, most notably cancer and diabetes. However, the causes and consequences of these abnormal vessels have not been elucidated. Here, we use intravital, high-resolution imaging to examine the formation, resolution, and sprouting of tortuous microvessels during wound healing. We found that tortuous microvessels are mainly located 100-300 μm from the wound center and that tortuous microvessels resolved by becoming normal again. Additionally, using fluorescent, microcarrier beads we found that beads became stuck in tortuous microvessels suggesting differences in flow. The shapes of endothelial cells within tortuous microvessels are round, indicative of activated cells, and exhibit sprout initiations at a higher frequency than normal vessels. Thus, we highlight an important, undiscovered feature of tortuous microvessels, sprouting, that can be used as a therapeutic target to normalize tortuous vessels during disease. 2017 Molecular biology Biology Genetics angiogenesis; BMP; intravital; tortuous microvessels; wound healing eng Doctor of Philosophy Dissertation Genetics and Molecular Biology Victoria Bautch Thesis advisor Kathleen Caron Thesis advisor Frank Conlon Thesis advisor John Rawls Thesis advisor Paul Dayton Thesis advisor text 2017-08 University of North Carolina at Chapel Hill Degree granting institution Diana Chong Creator Curriculum in Genetics and Molecular Biology School of Medicine SPROUTING ANGIOGENESIS DURING RETINAL DEVELOPMENT AND WOUND HEALING Endothelial cells, the cells that line blood vessels, become activated during development to sprout and form new vessels in a process termed angiogenesis. During development, sprouting angiogenesis is robust and is the main driving force behind vascularization of new tissues in the embryo. In contrast, endothelial cells are mainly quiescent in the adult and only become reactivated during physiological or pathological angiogenesis. The bone morphogenetic protein (BMP) pathway has been shown to be a pro-angiogenic cue. During postnatal retinal development, BMP receptors are expressed in the retinal vasculature and BMP ligands are expressed throughout the retina. Here, we show that deletion of BMP receptors, Alk1, Alk2, Alk3, and BMPR2 affect sprouting angiogenesis during development. Endothelial specific deletion of Alk2, Alk3, and BMPR2 resulted in decreased sprouting at the vascular front as well as branching in the vascular plexus, whereas deletion of Alk1 resulted in increased sprouting. These data point to a requirement of BMP signaling for proper patterning of the retinal vasculature during development. We also analyzed tortuous microvessels, abnormal vessels that arise during the wound healing process. Tortuous vessels are observed in many diseases, most notably cancer and diabetes. However, the causes and consequences of these abnormal vessels have not been elucidated. Here, we use intravital, high-resolution imaging to examine the formation, resolution, and sprouting of tortuous microvessels during wound healing. We found that tortuous microvessels are mainly located 100-300 μm from the wound center and that tortuous microvessels resolved by becoming normal again. Additionally, using fluorescent, microcarrier beads we found that beads became stuck in tortuous microvessels suggesting differences in flow. The shapes of endothelial cells within tortuous microvessels are round, indicative of activated cells, and exhibit sprout initiations at a higher frequency than normal vessels. Thus, we highlight an important, undiscovered feature of tortuous microvessels, sprouting, that can be used as a therapeutic target to normalize tortuous vessels during disease. 2017 Molecular biology Biology Genetics angiogenesis, BMP, intravital, tortuous microvessels, wound healing eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Genetics and Molecular Biology Victoria Bautch Thesis advisor Kathleen Caron Thesis advisor Frank Conlon Thesis advisor John Rawls Thesis advisor Paul Dayton Thesis advisor text 2017-08 Diana Chong Creator Curriculum in Genetics and Molecular Biology School of Medicine Endothelial cells, the cells that line blood vessels, become activated during development to sprout and form new vessels in a process termed angiogenesis. During development, sprouting angiogenesis is robust and is the main driving force behind vascularization of new tissues in the embryo. In contrast, endothelial cells are mainly quiescent in the adult and only become reactivated during physiological or pathological angiogenesis. The bone morphogenetic protein (BMP) pathway has been shown to be a pro-angiogenic cue. During postnatal retinal development, BMP receptors are expressed in the retinal vasculature and BMP ligands are expressed throughout the retina. Here, we show that deletion of BMP receptors, Alk1, Alk2, Alk3, and BMPR2 affect sprouting angiogenesis during development. Endothelial specific deletion of Alk2, Alk3, and BMPR2 resulted in decreased sprouting at the vascular front as well as branching in the vascular plexus, whereas deletion of Alk1 resulted in increased sprouting. These data point to a requirement of BMP signaling for proper patterning of the retinal vasculature during development. We also analyzed tortuous microvessels, abnormal vessels that arise during the wound healing process. Tortuous vessels are observed in many diseases, most notably cancer and diabetes. However, the causes and consequences of these abnormal vessels have not been elucidated. Here, we use intravital, high-resolution imaging to examine the formation, resolution, and sprouting of tortuous microvessels during wound healing. We found that tortuous microvessels are mainly located 100-300 μm from the wound center and that tortuous microvessels resolved by becoming normal again. Additionally, using fluorescent, microcarrier beads we found that beads became stuck in tortuous microvessels suggesting differences in flow. The shapes of endothelial cells within tortuous microvessels are round, indicative of activated cells, and exhibit sprout initiations at a higher frequency than normal vessels. Thus, we highlight an important, undiscovered feature of tortuous microvessels, sprouting, that can be used as a therapeutic target to normalize tortuous vessels during disease. 2017 Molecular biology Biology Genetics angiogenesis; BMP; intravital; tortuous microvessels; wound healing eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Victoria Bautch Thesis advisor Kathleen Caron Thesis advisor Frank Conlon Thesis advisor John Rawls Thesis advisor Paul Dayton Thesis advisor text 2017-08 Chong_unc_0153D_17232.pdf uuid:bf1ba062-6ff1-497d-acd3-da0ea9c98e5b proquest 2019-08-15T00:00:00 2017-07-13T19:18:34Z application/pdf 4097549 yes