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. 2010 Sep 2;467(7311):91-4.
doi: 10.1038/nature09334.

A spindle-independent cleavage furrow positioning pathway

Clemens Cabernard  1 , Kenneth E Prehoda, Chris Q Doe
Affiliations

A spindle-independent cleavage furrow positioning pathway

Clemens Cabernard et al. Nature. .

Abstract

The mitotic spindle determines the cleavage furrow site during metazoan cell division, but whether other mechanisms exist remains unknown. Here we identify a spindle-independent mechanism for cleavage furrow positioning in Drosophila neuroblasts. We show that early and late furrow proteins (Pavarotti, Anillin, and Myosin) are localized to the neuroblast basal cortex at anaphase onset by a Pins cortical polarity pathway, and can induce a basally displaced furrow even in the complete absence of a mitotic spindle. Rotation or displacement of the spindle results in two furrows: an early polarity-induced basal furrow and a later spindle-induced furrow. This spindle-independent cleavage furrow mechanism may be relevant to other highly polarized mitotic cells, such as mammalian neural progenitors.

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Figures

Figure 1
Figure 1. Polarized cortical localization of Pav/Myosin furrow markers
(a) Summary of cortical Pav/Myosin (green) localization during a representative symmetric cell division (left) or a neuroblast asymmetric cell division (right). Central spindle microtubules, black; astral microtubules, gray. (b) Basal cortical localization of endogenous Pav/Myosin proteins in mitotic neuroblasts. (c,d) Localization of Pav:GFP and Sqh:GFP (Myosin) from movies 1–3. Overlay is shown below single channel image sequence Bottom rows show cortical pixel intensity plots for each protein around one half of the neuroblast cortex: from apical center (top) to basal center (bottom) of cortex. Apical up, basal down. Myo: Myosin, MTs: Microtubules. Scale bars: 10μm. Time in min:sec from anaphase onset.
Figure 2
Figure 2. Spindle-independent cleavage furrow positioning
(a) Sas-4 mutant neuroblast lacks astral microtubules, yet still establishes basal Myosin localization and basal furrow position (100%, n=158). (b) Colcemid-treated rod mutant neuroblast lacks all spindle microtubules, yet still establishes basal Myosin localization and basal furrow position (100%, n=7). (c) Colcemid-treated wild type neuroblast lacks all spindle microtubules, remains arrested at metaphase, and does not establish basal Myosin localization or initiate furrow formation (100%, n=7). A schematic of each experiment is shown to the left (apical/basal polarity, blue/red; microtubules, gray). All genotypes imaged in late second/early third larval instar brains. Scale bars: 10μm. Time in min:sec.
Figure 3
Figure 3. Neuroblasts use both spindle-induced and polarity-induced furrow positioning pathways
(a) Schematic of experimental design. Apical/basal polarity, blue/red; spindle, grey. (b) Spindle displacement experiment: colcemid-treated neuroblast with tiny apical spindles form two spatiotemporally-distinct furrows. Early basal furrow (arrow); later spindle-associated furrow (arrowhead). (c–f) Spindle rotation experiment: mud mutant neuroblasts with spindles orthogonal to the apical-basal polarity axis form two spatiotemporally-distinct furrows. (c) Neuroblast forms an early basal furrow (arrow), followed by an orthogonal spindle-associated furrow (arrowhead). (d) Neuroblast forms an early basal furrow that pinches off an anucleate “polar lobe” (arrow). Cherry:Miranda marks the basal cortex. (e) Still pictures from movie 9 showing the basal contractile ring “en face” to document the progressive constriction of the contractile ring. Yellow arrows, basal furrow; white arrows, orthogonal spindle-associated contractile ring. (f) Summary of spindle rotation experiment. Myosin, green; spindle, black; midbody remnant, green dot. Time scale m:ss. Scale bar: 10μm.
Figure 4
Figure 4. Mechanism of polarity-induced furrow formation
(a) Basal Myosin localization in anaphase neuroblasts is normal in neuroblasts strongly depleted for Pavarotti (Pav), aPKC, Miranda (Mira; MARCM clones) or zygotic null Gαi mutants. In all panels, time stamp: m:ss. Scale bar: 10μm. (b) Zygotic pins single mutant larval neuroblast undergoing a symmetric division and showing symmetric Myosin (Sqh:GFP) localization. (c) Zygotic dlg single mutant anaphase larval neuroblast undergoing a symmetric division and showing symmetric Myosin (Sqh:GFP) localization. (d) Zygotic dlg pins double mutant anaphase neuroblast in early third larval instar undergoing a symmetric division and showing symmetric Myosin (Sqh:GFP) localization. (e) Summary.
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