25 research outputs found

    The last-born daughter cell contributes to division orientation of Drosophila larval neuroblasts

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    The highly proliferative neuroblasts of the Drosophila larval brain divide over many cell cycles in a polarized manner. Here the authors show that the orientation of the axis of NB divisions is defined by the position of their last-born daughter cell

    Notch Signaling:Where Is the Action?

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    It has been a long-standing question as to whether the activation of Notch by its ligands occurs in a specific region of the plasma membrane. A study now shows that this is indeed the case in the Drosophila sensory organ precursor cell lineage

    Requirement of the Dynein-Adaptor Spindly for Mitotic and Post-Mitotic Functions in Drosophila

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    Spindly was originally identified as a specific regulator of Dynein activity at the kinetochore. In early prometaphase, Spindly recruits the Dynein/Dynactin complex, promoting the establishment of stable kinetochore-microtubule interactions and progression into anaphase. While details of Spindly function in mitosis have been worked out in cultured human cells and in the C. elegans zygote, the function of Spindly within the context of an organism has not yet been addressed. Here, we present loss- and gain-of-function studies of Spindly using transgenic RNAi in Drosophila. Knock-down of Spindly in the female germ line results in mitotic arrest during embryonic cleavage divisions. We investigated the requirements of Spindly protein domains for its localisation and function, and found that the carboxy-terminal region controls Spindly localisation in a cell-type specific manner. Overexpression of Spindly in the female germ line is embryonic lethal and results in altered egg morphology. To determine whether Spindly plays a role in post-mitotic cells, we altered Spindly protein levels in migrating cells and found that ovarian border cell migration is sensitive to the levels of Spindly protein. Our study uncovers novel functions of Spindly and a differential, functional requirement for its carboxy-terminal region in Drosophila

    Stem cell decisions:A twist of fate or a niche market?

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    AbstractEstablishing and maintaining cell fate in the right place at the right time is a key requirement for normal tissue maintenance. Stem cells are at the core of this process. Understanding how stem cells balance self-renewal and production of differentiating cells is key for understanding the defects that underpin many diseases. Both, external cues from the environment and cell intrinsic mechanisms can control the outcome of stem cell division. The role of the orientation of stem cell division has emerged as an important mechanism for specifying cell fate decisions. Although, the alignment of cell divisions can dependent on spatial cues from the environment, maintaining stemness is not always linked to positioning of stem cells in a particular microenvironment or `niche'. Alternate mechanisms that could contribute to cellular memory include differential segregation of centrosomes in asymmetrically dividing cells

    aPKC regulates apical constriction to prevent tissue rupture in the Drosophila follicular epithelium

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    Funding: We thank Daniel St Johnston, Juergen Knoblich, Patrick Laprise, Stefano de Renzis, Xiaobo Wang, Yohanns Bellaiche, and the Bloomington and Kyoto Drosophila Stock Centers for reagents. We also thank Yohanns Bellaiche, Ivo Telley, and Romain Levayer for insightful comments on the manuscript. This work is funded by National Funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., under the project PTDC/BIA-CEL/ 1511/2021. E.M.-d.-S.’s salary is funded by the ‘‘FCT Scientific Employment Stimulus’’ program. M.O.,A.B.-C., and A.M.C. were supported by PhD fellowships from FCT. M.O.’s salary was also supported by the Maria de Sousa Award Research in the J.J. lab was supported by Wellcome Trust, the Royal Society, and BBSRC (BB/V001353/1). The authors acknowledge the i3S Scientific Platform ALM, member of the national infrastructure Portuguese Platform of Bioimaging, and the Dundee Imaging Facility for excellent support.Apical-basal polarity is an essential epithelial trait controlled by the evolutionarily conserved PAR-aPKC polarity network. Dysregulation of polarity proteins disrupts tissue organization during development and in disease, but the underlying mechanisms are unclear due to the broad implications of polarity loss. Here, we uncover how Drosophila aPKC maintains epithelial architecture by directly observing tissue disorganization after fast optogenetic inactivation in living adult flies and ovaries cultured ex vivo. We show that fast aPKC perturbation in the proliferative follicular epithelium produces large epithelial gaps that result from increased apical constriction, rather than loss of apical-basal polarity. Accordingly, we can modulate the incidence of epithelial gaps by increasing and decreasing actomyosin-driven contractility. We traced the origin of these large epithelial gaps to tissue rupture next to dividing cells. Live imaging shows that aPKC perturbation induces apical constriction in non-mitotic cells within minutes, producing pulling forces that ultimately detach dividing and neighboring cells. We further demonstrate that epithelial rupture requires a global increase of apical constriction, as it is prevented by the presence of non-constricting cells. Conversely, a global induction of apical tension through light-induced recruitment of RhoGEF2 to the apical side is sufficient to produce tissue rupture. Hence, our work reveals that the roles of aPKC in polarity and actomyosin regulation are separable and provides the first in vivo evidence that excessive tissue stress can break the epithelial barrier during proliferation.proofepub_ahead_of_prin
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