Ras signalling downstream of plexind1
Date
2012
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Abstract
Angiogenesis is a crucially important process necessary for the proper development of vertebrates. Aberrant angiogenesis is involved in a variety of diseases ranging from arteriovenus malformations to tumour vascularisation in cancer. Plexin-Semaphorin signalling provides guidance cues for migrating blood vessels and neurons. The activation of other Plexin family members is known to result in the de-activation of integrins - cell surface receptors that variably exhibit high or low binding affinities for the extra-cellular matrix. PlexinDl is an endothelial cell marker that when lost causes the disorganized growth of intersomitic blood vessels in mice and zebrafish. The PlexinD 1 -/- (out-of-bounds) phenotype has been previously characterized, but the downstream effectors of PlexinDl remain largely unknown. The intracellular component of Plexins contain a highly conserved R-RasGTPase Activating Protein motif. I hypothesized that if R-Ras was the immediate effector of PlexinDl, modulation of the GTPase activity of RĀRas or its related family member R-Ras2 would recapitulate the out-of-bounds phenotype observed in PlexinDl mutants. I found that R-Ras is not required for proper intersomitic vessel patterning and that over expression of a constitutively active R-Ras does not phenocopy out-of-bounds. Likewise I found that modulating R-Ras2 activity does not affect vascular patterning. I did find that the R-Rasi2e3 morpholino produces a strong, and even more severe out-of-bounds like phenotype, with additional ventral sprouting. This is a novel discovery which warrants further research into finding the target of this morpholino.
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Bibliography: p. 109-122
Includes copy of animal protocol approval. Original copy with original Partial Copyright Licence.
Includes copy of animal protocol approval. Original copy with original Partial Copyright Licence.
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Citation
Sobering, R. E. (2012). Ras signalling downstream of plexind1 (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/4555