Persistent Link:
http://hdl.handle.net/10150/194116
Title:
Role of Hedgehog Signaling on Endothelial Vascular Patterning
Author:
Moran, Carlos M.
Issue Date:
2010
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
During embryonic vasculogenesis, endothelial cells form in the mesoderm , assemble into cord-like structures and then undergo tube formation. Previous studies have shown that signaling by members of the hedgehog family of secreted growth factors is essential for normal development of embryonic blood vessels. Embryos lacking hedgehog function show the presence of abundant endothelial cells but the cells fail to assemble into vascular cords and lumenized endothelial tubes do not form. At present it is not known whether active hedgehog signaling is required for both cord and tube formation or only for the initial step. To address this question, we have used small molecule inhibitors and agonists to the alter activity of the hedgehog signaling pathway in the chick embryo. If development is allowed to proceed until endothelial cells of the future dorsal aortae have assembled into cords, subsequent inhibition of hedgehog signaling, using cyclopamine, does not prevent aortal cells from forming endothelial tubes, however, it does lead to a reduction in cross sectional area of the aorta and to a loss of density of the adjacent vascular plexus. In contrast, activation of the hedgehog pathway with SAG leads to formation of enlarged aortae and increased density of the plexus. Very little, if any, of the observed effects are due to differences in number of endothelial cells in the treated embryos. Examination of endothelial cells during vascular plexus formation shows that inhibition of hedgehog signaling with cyclopamine inhibits formation of filopodia while treatment with SAG increases the number of filopodial extensions. These studies show that hedgehog signaling levels must be tightly regulated for normal vascular patterning to be achieved.
Type:
text; Electronic Dissertation
Keywords:
cardiovascular; chick development; endothelial cells; hedgehog; vascular patterning; VEGF
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Cell Biology & Anatomy; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Krieg, Paul A.
Committee Chair:
Krieg, Paul A.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleRole of Hedgehog Signaling on Endothelial Vascular Patterningen_US
dc.creatorMoran, Carlos M.en_US
dc.contributor.authorMoran, Carlos M.en_US
dc.date.issued2010en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractDuring embryonic vasculogenesis, endothelial cells form in the mesoderm , assemble into cord-like structures and then undergo tube formation. Previous studies have shown that signaling by members of the hedgehog family of secreted growth factors is essential for normal development of embryonic blood vessels. Embryos lacking hedgehog function show the presence of abundant endothelial cells but the cells fail to assemble into vascular cords and lumenized endothelial tubes do not form. At present it is not known whether active hedgehog signaling is required for both cord and tube formation or only for the initial step. To address this question, we have used small molecule inhibitors and agonists to the alter activity of the hedgehog signaling pathway in the chick embryo. If development is allowed to proceed until endothelial cells of the future dorsal aortae have assembled into cords, subsequent inhibition of hedgehog signaling, using cyclopamine, does not prevent aortal cells from forming endothelial tubes, however, it does lead to a reduction in cross sectional area of the aorta and to a loss of density of the adjacent vascular plexus. In contrast, activation of the hedgehog pathway with SAG leads to formation of enlarged aortae and increased density of the plexus. Very little, if any, of the observed effects are due to differences in number of endothelial cells in the treated embryos. Examination of endothelial cells during vascular plexus formation shows that inhibition of hedgehog signaling with cyclopamine inhibits formation of filopodia while treatment with SAG increases the number of filopodial extensions. These studies show that hedgehog signaling levels must be tightly regulated for normal vascular patterning to be achieved.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectcardiovascularen_US
dc.subjectchick developmenten_US
dc.subjectendothelial cellsen_US
dc.subjecthedgehogen_US
dc.subjectvascular patterningen_US
dc.subjectVEGFen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineCell Biology & Anatomyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorKrieg, Paul A.en_US
dc.contributor.chairKrieg, Paul A.en_US
dc.contributor.committeememberGregorio, Carol C.en_US
dc.contributor.committeememberWilson, Jean M.en_US
dc.contributor.committeememberHeimark, Ronalden_US
dc.contributor.committeememberAntin, Parker B.en_US
dc.identifier.proquest11230en_US
dc.identifier.oclc752261099en_US
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