<i>Drosophila</i> aPKC is required for mitotic spindle orientation during symmetric division of epithelial cells

Guilgur, Leonardo G.; Prudêncio, Pedro; Ferreira, Tânia; Pimenta-Marques, Ana; Martinho, Rui Gonçalo

doi:10.1242/dev.071027

Cited by 58 publications

(57 citation statements)

References 42 publications

(64 reference statements)

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“…Egg chambers transheterozygous for apkc ts and the loss-of-function allele apkc k06403 , have cyst encapsulation defects at 25 ° that preclude the accurate measurement of mitotic spindle angles [8]. At 18 °, large regions of organized epithelium persist in most egg chambers, although 68% (n = 28) show some encapsulation defects (Figure 2G).…”

Section: Resultsmentioning

confidence: 99%

Discs Large Links Spindle Orientation to Apical-Basal Polarity in Drosophila Epithelia

2013

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SummaryMitotic spindles in epithelial cells are oriented in the plane of the epithelium so that both daughter cells remain within the monolayer, and defects in spindle orientation have been proposed to promote tumorigenesis by causing epithelial disorganization and hyperplasia [1]. Previous work has implicated the apical polarity factor aPKC, the junctional protein APC2, and basal integrins in epithelial spindle orientation, but the underlying mechanisms remain unclear. We show that these factors are not required for spindle orientation in the Drosophila follicular epithelium. Furthermore, aPKC and other apical polarity factors disappear from the apical membrane in mitosis. Instead, spindle orientation requires the lateral factor Discs large (Dlg), a function that is separable from its role in epithelial polarity. In neuroblasts, Pins recruits Dlg and Mud to form an apical complex that orients spindles along the apical-basal axis. We show that Pins and Mud are also necessary for spindle orientation in follicle cells, as is the interaction between Dlg and Pins. Dlg localizes independently of Pins, however, suggesting that its lateral localization determines the planar orientation of the spindle in epithelial cells. Thus, different mechanisms recruit the conserved Dlg/Pins/Mud complex to orient the spindle in opposite directions in distinct cell types.

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Section: Resultsmentioning

confidence: 99%

Discs Large Links Spindle Orientation to Apical-Basal Polarity in Drosophila Epithelia

2013

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“…PRKCZ is part of the apical Par complex comprising PARD3 and PARD6B and acts as a key regulator of mitotic spindle orientation in other systems (Durgan et al., 2011, Guilgur et al., 2012, Niessen et al., 2013). Of interest, the subcellular redistribution of PRKCZ is found in the presence of normal PARD3 and PARD6B apical expression, suggesting a decoupling of PRKCZ from the Par complex.…”

Section: Discussionmentioning

confidence: 99%

Lineage Specification from Prostate Progenitor Cells Requires Gata3-Dependent Mitotic Spindle Orientation

et al. 2017

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SummaryDuring prostate development, basal and luminal cell lineages are generated through symmetric and asymmetric divisions of bipotent basal cells. However, the extent to which spindle orientation controls division symmetry or cell fate, and the upstream factors regulating this process, are still elusive. We report that GATA3 is expressed in both prostate basal progenitor and luminal cells and that loss of GATA3 leads to a mislocalization of PRKCZ, resulting in mitotic spindle randomization during progenitor cell division. Inherently proliferative intermediate progenitor cells accumulate, leading to an expansion of the luminal compartment. These defects ultimately result in a loss of tissue polarity and defective branching morphogenesis. We further show that disrupting the interaction between PRKCZ and PARD6B is sufficient to recapitulate the spindle and cell lineage phenotypes. Collectively, these results identify a critical role for GATA3 in prostate lineage specification, and further highlight the importance of regulating spindle orientation for hierarchical cell lineage organization.

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“…In the symmetric divisions of epithelia, however, our data and others suggest spindle orientation is critical in maintaining cell viability (Nakajima et al, 2013). In both tissues, other polarity cues also contribute to spindle orientation (Basto et al, 2006; Guilgur et al, 2012; Nakajima et al, 2013). How do most acentrosomal spindles find their proper orientation?…”

Section: Discussionmentioning

confidence: 99%

Acentrosomal Drosophila Epithelial Cells Exhibit Abnormal Cell Division, Leading to Cell Death and Compensatory Proliferation

2014

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Summary Mitotic spindles are critical for accurate chromosome segregation. Centrosomes, the primary microtubule nucleating centers of animal cells, play key roles in forming and orienting mitotic spindles. However, the survival of Drosophila without centrosomes suggested they are dispensable in somatic cells, challenging the canonical view. We used fly wing disc epithelia as a model to resolve these conflicting hypotheses, revealing that centrosomes play vital roles in spindle assembly, function, and orientation. Many acentrosomal cells exhibit prolonged spindle assembly, chromosome mis-segregation, DNA damage, misoriented divisions, and eventual apoptosis. We found that multiple mechanisms buffer the effects of centrosome loss, including alternative microtubule nucleation pathways and the Spindle Assembly Checkpoint. Apoptosis of acentrosomal cells is mediated by JNK signaling, which also drives compensatory proliferation to maintain tissue integrity and viability. These data reveal the importance of centrosomes in fly epithelia, but also demonstrate the robust compensatory mechanisms at the cellular and organismal level.

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Drosophila aPKC is required for mitotic spindle orientation during symmetric division of epithelial cells

Cited by 58 publications

References 42 publications

Discs Large Links Spindle Orientation to Apical-Basal Polarity in Drosophila Epithelia

Discs Large Links Spindle Orientation to Apical-Basal Polarity in Drosophila Epithelia

Lineage Specification from Prostate Progenitor Cells Requires Gata3-Dependent Mitotic Spindle Orientation

Acentrosomal Drosophila Epithelial Cells Exhibit Abnormal Cell Division, Leading to Cell Death and Compensatory Proliferation

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