Apical junctions and growth control in Drosophila

Badouel, Caroline; McNeill, Helen

doi:10.1016/j.bbamem.2008.08.026

Cited by 9 publications

(5 citation statements)

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“…From apical to basal, the junction consists of a marginal zone (MZ), adherens junction (AJ) and septate junction (SJ) (Fig. 6B) (reviewed in Badouel and McNeill, 2009; Tepass et al, 2001). The center of a fold in the epithelium represents the juxtaposition of two apical surfaces, with lateral junctions spreading basally on both sides of the fold (schematic drawing in Fig.…”

Section: Resultsmentioning

confidence: 99%

Distinct tissue distributions and subcellular localizations of differently phosphorylated forms of the myosin regulatory light chain in Drosophila

Zhang

Ward

2011

Gene Expression Patterns

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Nonmuscle myosin II (myosin hereafter) has well-established roles in generating contractile force on actin filaments during morphogenetic processes in all metazoans. Myosin activation is regulated by phosphorylation of the myosin regulatory light chain (MRCL, encoded by spaghetti squash or sqh in Drosophila) first on Ser21 and subsequently on Thr20. These phosphorylation events are positively controlled by a variety of kinases including myosin light chain kinase, Rho kinase, citron kinase, and AMP kinase and are negatively regulated by myosin phosphatase. The activation of myosin is thus highly regulated and likely developmentally controlled. In order to monitor the activity of myosin during development, we have generated antibodies against the monophosphorylated (Sqh1P) and diphosphorylated (Sqh2P) forms of Sqh. We first show that the antibodies are highly specific. We then used these antibodies to monitor myosin activation in wild type Drosophila tissues. Interestingly, Sqh1P and Sqh2P show distinct patterns of expression in embryos. Sqh1P is expressed nearly ubiquitously and outlines cells consistent with a junctional localization, whereas Sqh2P is strongly expressed on the apical surfaces and in filopodia of tissues undergoing extensive cell shape change or cell movements including the invaginating fore-and hindgut, the invaginating tracheal system, the dorsal pouch and the dorsal most row of epidermal (DME) cells during dorsal closure. In imaginal discs, Sqh1P predominantly localizes in the adherens junction, whereas Sqh2P locates to the apical domain. These antibodies thus have the potential to be very useful in monitoring myosin activation for functional studies of morphogenesis in Drosophila. KeywordsDrosophila; myosin; myosin regulatory light chain; spaghetti squash; dorsal closure; morphogenesis Results and DiscussionNonmuscle myosin II (referred to as myosin hereafter) is a motor protein that binds reversibly to actin filaments and generates contractile forces necessary for a variety of © 2010 Elsevier B.V. All rights reserved. 3 Corresponding author: Robert E. Ward IV, Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Ave., Lawrence, Kansas 66045, robward@ku.edu, Phone: (785) Fax: (785) 864-5294. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptGene Expr Patterns. Author manuscript; available in PMC 2012 January 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript cellular processes including cell shape changes, cell movements, cytokinesis, maintenance of cell morpho...

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Section: Resultsmentioning

confidence: 99%

Distinct tissue distributions and subcellular localizations of differently phosphorylated forms of the myosin regulatory light chain in Drosophila

Zhang

Ward

2011

Gene Expression Patterns

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“…The WW-domain of YAP also interacts with the PPPY motif of the p73 (Strano et al, 2005). In Drosophila , direct interaction of Yki via its WW-domains with the PPxY motif of Ex, Wts and Hpo regulate pathway activity by sequestering Yki in protein complexes by the apical membrane (Badouel and McNeill, 2009; Badouel et al, 2009; Oh et al, 2009). In phosphorylation-independent regulation of Yki, overexpression of PPxY motif of Ex and Wts suppressed Yki mediated transcriptional activation regardless of mutation of the Wts phosphorylation site on Yki (Oh and Irvine, 2009; Oh et al, 2009; Ren et al, 2010).…”

Section: Hippo Signaling In Drosophila and Mammalsmentioning

confidence: 99%

“…For example, Mer and Kibra can bind to Sav, whilst Ex binds to Hpo, and Kibra binds to Wts (Baumgartner et al, 2010; Genevet et al, 2010; Yu et al, 2010). In addition to binding to the Hippo kinase cascade, Kibra can also bind to Yki, thus keeping Yki in the cytoplasm (Badouel and McNeill, 2009; Badouel et al, 2009; Oh et al, 2009). Drosophila Crumbs (Crb), a cell surface regulator for the Hippo pathway, has an intracellular FERM-binding domain that binds to Ex and controls its stability and localization, thus impacting its activity on Hpo kinases and Yki (Chen et al, 2010; Grzeschik et al, 2010; Ling et al, 2010; Robinson et al, 2010; Varelas et al, 2010).…”

Section: Upstream Regulators Of Hippo Pathwaymentioning

confidence: 99%

Hippo Signaling in Cancer: Lessons From Drosophila Models

Snigdha

Gangwani

Lapalikar

et al. 2019

Front. Cell Dev. Biol.

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Hippo pathway was initially identified through genetic screens for genes regulating organ size in fruitflies. Recent studies have highlighted the role of Hippo signaling as a key regulator of homeostasis, and in tumorigenesis. Hippo pathway is comprised of genes that act as tumor suppressor genes like hippo ( hpo ) and warts ( wts ), and oncogenes like yorkie ( yki ). YAP and TAZ are two related mammalian homologs of Drosophila Yki that act as effectors of the Hippo pathway. Hippo signaling deficiency can cause YAP- or TAZ-dependent oncogene addiction for cancer cells. YAP and TAZ are often activated in human malignant cancers. These transcriptional regulators may initiate tumorigenic changes in solid tumors by inducing cancer stem cells and proliferation, culminating in metastasis and chemo-resistance. Given the complex mechanisms (e.g., of the cancer microenvironment, and the extrinsic and intrinsic cues) that overpower YAP/TAZ inhibition, the molecular roles of the Hippo pathway in tumor growth and progression remain poorly defined. Here we review recent findings from studies in whole animal model organism like Drosophila on the role of Hippo signaling regarding its connection to inflammation, tumor microenvironment, and other oncogenic signaling in cancer growth and progression.

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“…Dlg binds to Scrib [34] and all three are required for the proper organization and localization of other apical-basal polarity genes. Recent studies indicate that the neoplastic tumor suppressor genes directly regulate cell proliferation of epithelial cells, rather than indirectly through effects on the localization of growth factor receptors [35], [36], [37], because hypomorphic conditions for Lgl and Dlg, for example, affect growth without affecting cell polarity [38], [39].…”

Section: Introductionmentioning

confidence: 99%

Scribble Acts in the Drosophila Fat-Hippo Pathway to Regulate Warts Activity

et al. 2012

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Epithelial cells are the major cell-type for all organs in multicellular organisms. In order to achieve correct organ size, epithelial tissues need mechanisms that limit their proliferation, and protect tissues from damage caused by defective epithelial cells. Recently, the Hippo signaling pathway has emerged as a major mechanism that orchestrates epithelial development. Hippo signaling is required for cells to stop proliferation as in the absence of Hippo signaling tissues continue to proliferate and produce overgrown organs or tumors. Studies in Drosophila have led the way in providing a framework for how Hippo alters the pattern of gene transcription in target cells, leading to changes in cell proliferation, survival, and other behaviors. Scribble (Scrib) belongs to a class of neoplastic tumor suppressor genes that are required to establish apical-basal cell polarity. The disruption of apical-basal polarity leads to uncontrolled cell proliferation of epithelial cells. The interaction of apical basal polarity genes with the Hippo pathway has been an area of intense investigation. Loss of scrib has been known to affect Hippo pathway targets, however, its functions in the Hippo pathway still remain largely unknown. We investigated the interactions of Scrib with the Hippo pathway. We present data suggesting that Drosophila scrib acts downstream of the Fat (Ft) receptor, and requires Hippo signaling for its growth regulatory functions. We show that Ft requires Scrib to interact with Expanded (Ex) and Dachs (D), and for regulating Warts (Wts) levels and stability, thus placing Scrib in the Hippo pathway network.

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Apical junctions and growth control in Drosophila

Cited by 9 publications

References 79 publications

Distinct tissue distributions and subcellular localizations of differently phosphorylated forms of the myosin regulatory light chain in Drosophila

Distinct tissue distributions and subcellular localizations of differently phosphorylated forms of the myosin regulatory light chain in Drosophila

Hippo Signaling in Cancer: Lessons From Drosophila Models

Scribble Acts in the Drosophila Fat-Hippo Pathway to Regulate Warts Activity

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