scholarly journals Interaction between Discs large and Pins/LGN/GPSM2: A comparison across species

Biology Open ◽  
2021 ◽  
Author(s):  
Emily A. Schiller ◽  
Dan T. Bergstralh
Keyword(s):  
Cell Fate ◽  
Mitotic Spindle ◽  
Evolutionary History ◽  
Scaffolding Protein ◽  
Spindle Orientation ◽  
C Elegans ◽  
Discs Large ◽  
Canonical Pathways ◽  
History Of ◽  
Multicellular Organisms

The orientation of the mitotic spindle determines the direction of cell division, and therefore contributes to tissue shape and cell fate. Interaction between the multifunctional scaffolding protein Discs large (Dlg) and the canonical spindle orienting factor GPSM2 (called Pins in Drosophila and LGN in vertebrates) has been established in bilaterian models, but its function remains unclear. We used a phylogenetic approach to test whether the interaction is obligate in animals, and in particular whether Pins/LGN/GPSM2 evolved in multicellular organisms as a Dlg-binding protein. We show that Dlg diverged in C. elegans and the syncytial sponge O. minuta and propose that this divergence may correspond to differences in spindle orientation requirements between these organisms and the canonical pathways described in bilaterians. We also demonstrate that Pins/LGN/GPSM2 is present in basal animals, but the established Dlg-interaction site cannot be found in either Placozoa or Porifera. Our results suggest that the interaction between Pins/LGN/GPSM2 and Dlg appeared in Cnidaria, and we therefore speculate that it may have evolved to promote accurate division orientation in the nervous system. This work reveals the evolutionary history of the Pins/LGN/GPSM2-Dlg interaction and suggests new possibilities for its importance in spindle orientation during epithelial and neural tissue development.

scholarly journals Interaction between Discs large and GPSM2: A Comparison Across Species

2021 ◽  
Author(s):  
Emily Schiller ◽  
Dan T Bergstralh
Keyword(s):  
Cell Fate ◽  
Mitotic Spindle ◽  
Evolutionary History ◽  
Scaffolding Protein ◽  
Spindle Orientation ◽  
C Elegans ◽  
Discs Large ◽  
Canonical Pathways ◽  
History Of ◽  
Multicellular Organisms

The orientation of the mitotic spindle determines the direction of cell division, and therefore contributes to tissue shape and cell fate. Interaction between the multifunctional scaffolding protein Discs large (Dlg) and the canonical spindle orienting factor GPSM2 (also called Pins in Drosophila and LGN in vertebrates) has been established in bilaterian models, but its function remains unclear. We used a phylogenetic approach to test whether the interaction is obligate in animals, and in particular whether GPSM2 evolved in multicellular organisms as a Dlg-binding protein. We show that Dlg diverged in C. elegans and the syncytial sponge O. minuta and propose that this divergence may correspond to differences in spindle orientation requirements between these organisms and the canonical pathways described in bilaterians. We also demonstrate that GPSM2 is present in basal animals, but the established Dlg-interaction site cannot be found in either Placozoa or Porifera. Our results suggest that the interaction between GPSM2 and Dlg appeared in Cnidaria, and we therefore speculate that it may have evolved to promote accurate division orientation in the nervous system. This work reveals the evolutionary history of the GPSM2/Dlg interaction and suggests new possibilities for its importance in spindle orientation during epithelial and neural tissue development.

scholarly journals Junctional tumor suppressors interact with 14-3-3 proteins to control planar spindle alignment

2019 ◽  
Vol 218 (6) ◽  
pp. 1824-1838 ◽  
Author(s):  
Yu-ichiro Nakajima ◽  
Zachary T. Lee ◽  
Sean A. McKinney ◽  
Selene K. Swanson ◽  
Laurence Florens ◽  
...  
Keyword(s):  
Cell Fate ◽  
Tumor Suppressors ◽  
Mitotic Spindle ◽  
Wing Disc ◽  
Spindle Orientation ◽  
Epithelial Proliferation ◽  
Tissue Architecture ◽  
Drosophila Wing ◽  
Discs Large

Proper orientation of the mitotic spindle is essential for cell fate determination, tissue morphogenesis, and homeostasis. During epithelial proliferation, planar spindle alignment ensures the maintenance of polarized tissue architecture, and aberrant spindle orientation can disrupt epithelial integrity. Nevertheless, in vivo mechanisms that restrict the mitotic spindle to the plane of the epithelium remain poorly understood. Here we show that the junction-localized tumor suppressors Scribbled (Scrib) and Discs large (Dlg) control planar spindle orientation via Mud and 14-3-3 proteins in the Drosophila wing disc epithelium. During mitosis, Scrib is required for the junctional localization of Dlg, and both affect mitotic spindle movements. Using coimmunoprecipitation and mass spectrometry, we identify 14-3-3 proteins as Dlg-interacting partners and further report that loss of 14-3-3s causes both abnormal spindle orientation and disruption of epithelial architecture as a consequence of basal cell delamination and apoptosis. Combined, these biochemical and genetic analyses indicate that 14-3-3s function together with Scrib, Dlg, and Mud during planar cell division.

scholarly journals NuMA-microtubule interactions are critical for spindle orientation and the morphogenesis of diverse epidermal structures

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Lindsey Seldin ◽  
Andrew Muroyama ◽  
Terry Lechler
Keyword(s):  
Cell Fate ◽  
Mitotic Spindle ◽  
Cell Types ◽  
Epidermal Differentiation ◽  
Spindle Orientation ◽  
Direct Function ◽  
Spindle Positioning ◽  
Adult Mice ◽  
Neonatal Lethality ◽  
The Matrix

Mitotic spindle orientation is used to generate cell fate diversity and drive proper tissue morphogenesis. A complex of NuMA and dynein/dynactin is required for robust spindle orientation in a number of cell types. Previous research proposed that cortical dynein/dynactin was sufficient to generate forces on astral microtubules (MTs) to orient the spindle, with NuMA acting as a passive tether. In this study, we demonstrate that dynein/dynactin is insufficient for spindle orientation establishment in keratinocytes and that NuMA’s MT-binding domain, which targets MT tips, is also required. Loss of NuMA-MT interactions in skin caused defects in spindle orientation and epidermal differentiation, leading to neonatal lethality. In addition, we show that NuMA-MT interactions are also required in adult mice for hair follicle morphogenesis and spindle orientation within the transit-amplifying cells of the matrix. Loss of spindle orientation in matrix cells results in defective differentiation of matrix-derived lineages. Our results reveal an additional and direct function of NuMA during mitotic spindle positioning, as well as a reiterative use of spindle orientation in the skin to build diverse structures.

scholarly journals Eph signaling controls mitotic spindle orientation and cell proliferation in neuroepithelial cells

2019 ◽  
Vol 218 (4) ◽  
pp. 1200-1217 ◽  
Author(s):  
Maribel Franco ◽  
Ana Carmena
Keyword(s):  
Cell Proliferation ◽  
Cell Fate ◽  
Mitotic Spindle ◽  
Optic Lobe ◽  
Spindle Orientation ◽  
Intercellular Signaling ◽  
Neuroepithelial Cells ◽  
Core Components ◽  
Conserved Core ◽  
Activity Dependent

Mitotic spindle orientation must be tightly regulated during development and adult tissue homeostasis. It determines cell-fate specification and tissue architecture during asymmetric and symmetric cell division, respectively. Here, we uncover a novel role for Ephrin–Eph intercellular signaling in controlling mitotic spindle alignment in Drosophila optic lobe neuroepithelial cells through aPKC activity–dependent myosin II regulation. We show that conserved core components of the mitotic spindle orientation machinery, including Discs Large1, Mud/NuMA, and Canoe/Afadin, mislocalize in dividing Eph mutant neuroepithelial cells and produce spindle alignment defects in these cells when they are down-regulated. In addition, the loss of Eph leads to a Rho signaling–dependent activation of the PI3K–Akt1 pathway, enhancing cell proliferation within this neuroepithelium. Hence, Eph signaling is a novel extrinsic mechanism that regulates both spindle orientation and cell proliferation in the Drosophila optic lobe neuroepithelium. Similar mechanisms could operate in other Drosophila and vertebrate epithelia.

scholarly journals The Signaling Network Controlling C. elegans Vulval Cell Fate Patterning

2018 ◽  
Vol 6 (4) ◽  
pp. 30 ◽  
Author(s):  
Hanna Shin ◽  
David Reiner
Keyword(s):  
Cell Fate ◽  
Signaling Network ◽  
Signaling Cascades ◽  
Cell Fates ◽  
C Elegans ◽  
Differentiated Cells ◽  
Vulval Precursor Cells ◽  
Cell Patterns ◽  
History Of ◽  
Anchor Cell

EGF, emitted by the Anchor Cell, patterns six equipotent C. elegans vulval precursor cells to assume a precise array of three cell fates with high fidelity. A group of core and modulatory signaling cascades forms a signaling network that demonstrates plasticity during the transition from naïve to terminally differentiated cells. In this review, we summarize the history of classical developmental manipulations and molecular genetics experiments that led to our understanding of the signals governing this process, and discuss principles of signal transduction and developmental biology that have emerged from these studies.

scholarly journals Mitotic spindle (DIS)orientation and DISease: Cause or consequence?

2012 ◽  
Vol 199 (7) ◽  
pp. 1025-1035 ◽  
Author(s):  
Anna Noatynska ◽  
Monica Gotta ◽  
Patrick Meraldi
Keyword(s):  
Cell Proliferation ◽  
Cell Fate ◽  
Mitotic Spindle ◽  
Brain Diseases ◽  
Spindle Orientation ◽  
Cell Fate Determination ◽  
Cellular Functions ◽  
Tissue Organization ◽  
Asymmetric Divisions ◽  
Correct Alignment

Correct alignment of the mitotic spindle during cell division is crucial for cell fate determination, tissue organization, and development. Mutations causing brain diseases and cancer in humans and mice have been associated with spindle orientation defects. These defects are thought to lead to an imbalance between symmetric and asymmetric divisions, causing reduced or excessive cell proliferation. However, most of these disease-linked genes encode proteins that carry out multiple cellular functions. Here, we discuss whether spindle orientation defects are the direct cause for these diseases, or just a correlative side effect.

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