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The RhoGAPs RGA-8/RICH-1/SH3BP1 and HUM-7/Myo9 regulate actomyosin enrichment during C. elegans embryonic morphogenesis
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TitleInfo
Title
The RhoGAPs RGA-8/RICH-1/SH3BP1 and HUM-7/Myo9 regulate actomyosin enrichment during C. elegans embryonic morphogenesis
Name
(type = personal)
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(type = family)
Raduwan
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Hamidah
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(type = date)
1988-
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Hamidah Raduwan
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(authority = RULIB)
author
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Irvine
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Kenneth
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Kenneth Irvine
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Advisory Committee
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chair
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Soto
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Martha
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Martha Soto
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Advisory Committee
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internal member
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Wadsworth
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William
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William Wadsworth
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Advisory Committee
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(authority = RULIB)
internal member
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Bennett
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Joan
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Joan Bennett
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Advisory Committee
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outside member
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Rutgers University
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degree grantor
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School of Graduate Studies
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Text
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theses
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2019
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2019-01
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2019
Place
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xx
Language
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eng
Abstract
(type = abstract)
Organ and tissue formation are highly regulated processes during embryonic development. Defects in this process can lead to birth defects, or premature death. The complexity of vertebrate tissues complicates the study of organ and tissue embryonic development. Epidermal morphogenesis in the nematode Caenorhabditis elegans is an ideal model to study tissue morphogenesis in whole organisms. C. elegans is amenable to genetics and microscopy observation, allowing us to capture live imaging of the migrating tissues. Previous studies from our lab identified a Rac1-dependent branched actin pathway as an important regulator of epidermal cell migration during this process. However, the role of actomyosin contractility during this process was unclear. Actin dynamics and actomyosin contractility are regulated by the Rho GTPases protein family. Rac1 and Cdc42 promote branched actin formation, while Cdc42 and RhoA promote actomyosin contractility. Rho GTPases are molecular switches that become activated by binding to GTP, and deactivated by hydrolyzing GTP to become GDP. The cycle of GTP- and GDP- binding is regulated by GTP exchange factor proteins (GEFs) and GTPase-activating proteins (GAPs), respectively. C. elegans only has seven members of Rho GTPases, but 23 GAPs, suggesting layers of regulation in
ii
the process of branched actin formation and actomyosin contractility. In this study we performed the first characterization of two RhoGAPs, RGA-8/RICH-1/SH3BP1 and HUM-7/Myo9 and show that they regulate morphogenesis in C. elegans by modulating RHO-1/RhoA and CDC-42. We show that RGA-8/RICH-1/SH3BP1 and HUM-7/Myo9 regulate myosin enrichment during morphogenesis, including at the epidermal pocket cells during ventral enclosure. Previous studies proposed actomyosin contractility is mainly required in underlying neuroblasts to promote epidermal cell migrations. In contrast, the results here show that myosin is polarized, and tightly regulated in the migrating epidermal cells, by RGA-8/RICH- 1/SH3BP1 and HUM-7/Myo9. In addition, we show these proteins contribute to normal morphogenesis by regulating the timing of morphogenetic cell movements. Overall, we place the RhoGAPs HUM-7/Myo9 and RGA-8/RICH-1/SH3BP1 in pathways that regulate both actin and actomyosin contractility through RHO-1 and CDC-42, demonstrating new roles for these GTPases in embryonic epidermal morphogenesis in C. elegans.
ii
the process of branched actin formation and actomyosin contractility. In this study we performed the first characterization of two RhoGAPs, RGA-8/RICH-1/SH3BP1 and HUM-7/Myo9 and show that they regulate morphogenesis in C. elegans by modulating RHO-1/RhoA and CDC-42. We show that RGA-8/RICH-1/SH3BP1 and HUM-7/Myo9 regulate myosin enrichment during morphogenesis, including at the epidermal pocket cells during ventral enclosure. Previous studies proposed actomyosin contractility is mainly required in underlying neuroblasts to promote epidermal cell migrations. In contrast, the results here show that myosin is polarized, and tightly regulated in the migrating epidermal cells, by RGA-8/RICH- 1/SH3BP1 and HUM-7/Myo9. In addition, we show these proteins contribute to normal morphogenesis by regulating the timing of morphogenetic cell movements. Overall, we place the RhoGAPs HUM-7/Myo9 and RGA-8/RICH-1/SH3BP1 in pathways that regulate both actin and actomyosin contractility through RHO-1 and CDC-42, demonstrating new roles for these GTPases in embryonic epidermal morphogenesis in C. elegans.
Subject
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Topic
Cell and Developmental Biology
Subject
(authority = ETD-LCSH)
Topic
Caenorhabditis elegans
Subject
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Topic
Morphogenesis
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Rutgers University Electronic Theses and Dissertations
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ETD_9541
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electronic resource
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application/pdf
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1 online resource (153 pages) : illustrations
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Ph.D.
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Includes bibliographical references
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Includes vita
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by Hamidah Raduwan
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School of Graduate Studies Electronic Theses and Dissertations
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rucore10001600001
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doi:10.7282/t3-jtzz-jp28
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ETD doctoral
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The author owns the copyright to this work.
RightsHolder
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Name
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Raduwan
GivenName
Hamidah
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Permission or license
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2019-01-23 16:57:11
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Hamidah Raduwan
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Rutgers University. School of Graduate Studies
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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2019-01-31
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2019-08-02
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after August 2nd, 2019.
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Copyright protected
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Open
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Permission or license
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windows xp
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2019-01-24T16:08:26
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