Adherens Junctions and The Actomyosin Network Regulate Organ Growth By Modulating Hippo Pathway Activity In Drosophila

<p>Adherens junctions (AJs) and basolateral modules are important for the establishment and maintenance of apico-basal polarity. Loss of AJs and basolateral module members lead to tumor formation, as well as poor prognosis for metastasis. Recently, in mammalian studies it has been shown that loss of either AJ or basolateral module members deregulate Yorkie activity, the downstream transcriptional effector of the Hippo pathway. Importantly, it is unclear if AJ and basolateral components act through the same or parallel mechanisms to regulate Yorkie activity.</p> <p>Here, we dissect how loss of AJ and basolateral components affects Hippo signaling in <em>Drosophila</em>. Surprisingly, while <em>scrib</em> knock-down tissue displays increased reporter activity autonomously, <em>α-cat</em> knock-down tissue shows a cell autonomous decrease and a cell non-autonomous increase of Hippo reporter activity. We provided several lines of evidence to show the differential regulation in polarity protein localizations and oncogenic cooperative overgrowth by AJs and basolateral complexes. Finally, we show that Hippo pathway activity is induced in <em>α-cat </em>and <em>scrib</em> double knocked-down tissue. Taken together, our results provide evidence to show that basolateral modules and AJs act in parallel to modulate Hippo pathway activity.</p> <p>Non-muscle myosin II is an actomyosin component that interacts with the actin. Non-muscle myosin II also interacts with lgl, though the function of this interaction is not clear. Our lab demonstrated that modulating F-actin regulates Hippo pathway activity, and <em>lgl</em> also has been described as a Hippo pathway regulator. Therefore we suspect that myosin II is also involved in Hippo pathway regulation.</p> <p>We first characterized non-muscle Myosin II as a novel tumor suppressor gene by affecting Hippo pathway activity. Upstream regulators of Myosin II, members in the Rho signaling pathway, also displayed similar phenotypes as the Myosin II knock-down tissues. Apoptosis is also induced in myosin II knock-down tissues, however, blocking cell death does not affect myosin II knock-down induced Hippo activation. Our data suggested hyperactivating myosin II induced F-actin accumulation so therefore induces Hippo target activation. Unexpectedly, we also observed that reducing F-actin activity induced Hippo target activation in vivo. These controversial data indicated that actomyosin may regulate the Hippo pathway through multiple mechanisms.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2012

Author dc:creator

• Yang, Chih-Chao

Contributors dc:contributor

• Halder, Georg
• Galko, Michael
• Jafar-Nejad, Hamed

• Hippo pathways
• adherens junctions
• polarity
• growth control
• actomyosin
• cytoskeleton
• Cell and Developmental Biology

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/287

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1321