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      Somatic support cells regulate germ cell survival through the Baz/aPKC/Par6 complex

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          ABSTRACT

          Local signals and structural support from the surrounding cellular microenvironment play key roles in directing development in both embryonic organs and adult tissues. In Drosophila, male germ cells are intimately associated and co-differentiate with supporting somatic cells. Here, we show that the function of the Baz/aPKC/Par6 apical polarity complex in somatic cyst cells is required stage specifically for survival of the germ cells they enclose. Although spermatogonia enclosed by cyst cells in which the function of the Par complex had been knocked down survived and proliferated, newly formed spermatocytes enclosed by cyst cells lacking Par complex proteins died soon after onset of meiotic prophase. Loss of Par complex function resulted in stage-specific overactivation of the Jun-kinase (JNK) pathway in cyst cells. Knocking down expression of JNK pathway components or the GTPase Rab35 in cyst cells lacking Par complex function rescued the survival of neighboring spermatocytes, suggesting that action of the apical polarity complex ensures germ cell survival by preventing JNK pathway activation, and that the mechanism by which cyst cells lacking Par complex function kill neighboring spermatocytes requires intracellular trafficking in somatic cyst cells.

          Abstract

          Summary: The Par polarity complex suppresses JNK pathway activity in Drosophila somatic support cells to allow stage-specific germ cell survival.

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          Most cited references33

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          Dynamics of adherens junctions in epithelial establishment, maintenance, and remodeling

          The epithelial cadherin (E-cadherin)–catenin complex binds to cytoskeletal components and regulatory and signaling molecules to form a mature adherens junction (AJ). This dynamic structure physically connects neighboring epithelial cells, couples intercellular adhesive contacts to the cytoskeleton, and helps define each cell’s apical–basal axis. Together these activities coordinate the form, polarity, and function of all cells in an epithelium. Several molecules regulate AJ formation and integrity, including Rho family GTPases and Par polarity proteins. However, only recently, with the development of live-cell imaging, has the extent to which E-cadherin is actively turned over at junctions begun to be appreciated. This turnover contributes to junction formation and to the maintenance of epithelial integrity during tissue homeostasis and remodeling.
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            armadillo, bazooka, and stardust are critical for early stages in formation of the zonula adherens and maintenance of the polarized blastoderm epithelium in Drosophila

            Cellularization of the Drosophila embryo results in the formation of a cell monolayer with many characteristics of a polarized epithelium. We have used antibodies specific to cellular junctions and nascent plasma membranes to study the formation of the zonula adherens (ZA) in relation to the establishment of basolateral membrane polarity. The same approach was then used as a test system to identify X-linked zygotically active genes required for ZA formation. We show that ZA formation begins during cellularization and that the basolateral membrane domain is established at mid-gastrulation. By creating deficiencies for defined regions of the X chromosome, we have identified genes that are required for the formation of the ZA and the generation of basolateral membrane polarity. We show that embryos mutant for both stardust (sdt) and bazooka (baz) fail to form a ZA. In addition to the failure to establish the ZA, the formation of the monolayered epithelium is disrupted after cellularization, resulting in formation of a multilayered cell sheet by mid-gastrulation. SEM analysis of mutant embryos revealed a conversion of cells exhibiting epithelial characteristics into cells exhibiting mesenchymal characteristics. To investigate how mutations that affect an integral component of the ZA itself influence ZA formation, we examined embryos with reduced maternal and zygotic supply of wild-type Arm protein. These embryos, like embryos mutant for both sdt and baz, exhibit an early disruption of ZA formation. These results suggest that early stages in the assembly of the ZA are critical for the stability of the polarized blastoderm epithelium.
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              Apoptosis-induced compensatory proliferation. The Cell is dead. Long live the Cell!

              In multi-cellular organisms, activation of apoptosis can trigger compensatory proliferation in surrounding cells to maintain tissue homeostasis. Genetic studies in Drosophila have indicated that distinct mechanisms of compensatory proliferation are employed in apoptotic tissues of different developmental states. In proliferating eye and wing tissues, the initiator caspase Dronc coordinates cell death and compensatory proliferation through the Jun N-terminal kinase and p53. The mitogens Decapentaplegic and Wingless are induced in this process. By contrast, in differentiating eye tissues, the effector caspases DrICE and Dcp-1 activate the Hedgehog signaling pathway to induce compensatory proliferation. In this review, we summarize these findings and discuss how activation of apoptosis is linked to the process of compensatory proliferation. The developmental and pathological relevance of compensatory proliferation is also discussed.
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                Author and article information

                Journal
                Development
                Development
                DEV
                develop
                Development (Cambridge, England)
                The Company of Biologists Ltd
                0950-1991
                1477-9129
                15 April 2019
                15 April 2019
                15 April 2019
                : 146
                : 8
                : dev169342
                Affiliations
                Department of Developmental Biology, Stanford University School of Medicine , Stanford, CA 94305, USA
                Author notes
                [* ]Author for correspondence ( mtfuller@ 123456stanford.edu )
                Author information
                http://orcid.org/0000-0002-3804-4987
                Article
                DEV169342
                10.1242/dev.169342
                6503986
                30918053
                ab0668a4-026d-42ad-8d43-7329bdf5f215
                © 2019. Published by The Company of Biologists Ltd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 26 June 2018
                : 21 March 2019
                Funding
                Funded by: National Science Foundation, http://dx.doi.org/10.13039/100000001;
                Funded by: American Heart Association, http://dx.doi.org/10.13039/100000968;
                Funded by: National Institutes of Health;
                Award ID: R01 GM080501
                Categories
                Research Article

                Developmental biology
                drosophila,spermatogenesis,cyst cells,par complex,jnk
                Developmental biology
                drosophila, spermatogenesis, cyst cells, par complex, jnk

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