The coordination of spindle‐positioning forces during the asymmetric division of theCaenorhabditis eleganszygote

AbstractThe PAR-1 kinase of C. elegans is localized to the posterior of the one-cell embryo and its mutations affect asymmetric spindle placement and partitioning of cytoplasmic components in the first cell cycle. However, unlike mutations in the posteriorly localized PAR-2 protein, par-1 mutations do not cause failure to restrict the anterior PAR polarity complex. Further, it has been difficult to examine the role of PAR-1 in subsequent divisions due to the early defects in par-1 mutant embryos. Here we show that the PIG-1 kinase acts redundantly with PAR-1 to restrict the anterior PAR-3 protein for polarity maintenance in the one-cell embryo. By using a weak allele of par-1 that exhibits enhanced lethality when combined with a pig-1 mutation we have further explored roles for these genes in subsequent divisions. We find that both PIG-1 and PAR-1 regulate spindle orientation in the EMS blastomere of the four-cell stage embryo to ensure that it undergoes an asymmetric division. In this cell, PIG-1 and PAR-1 act in parallel pathways for spindle positioning, PIG-1 in the MES-1/SRC-1 pathway and PAR-1 in the Wnt pathway.

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LET-99 functions in the astral furrowing pathway, where it is required for myosin enrichment in the contractile ring

Molecular Biology of the Cell ◽

10.1091/mbc.e16-12-0874 ◽

2017 ◽

Vol 28 (18) ◽

pp. 2360-2373 ◽

Cited By ~ 3

Author(s):

Kari L. Price ◽

Lesilee S. Rose

Keyword(s):

Asymmetric Division ◽

Contractile Ring ◽

Spindle Positioning ◽

Feedback Model ◽

Spindle Poles ◽

Dividing Cells ◽

Cell Embryo ◽

Cortical Localization ◽

Dependent Pathway

The anaphase spindle determines the position of the cytokinesis furrow, such that the contractile ring assembles in an equatorial zone between the two spindle poles. Contractile ring formation is mediated by RhoA activation at the equator by the centralspindlin complex and midzone microtubules. Astral microtubules also inhibit RhoA accumulation at the poles. In the Caenorhabditis elegans one-cell embryo, the astral microtubule–dependent pathway requires anillin, NOP-1, and LET-99. LET-99 is well characterized for generating the asymmetric cortical localization of the Gα-dependent force-generating complex that positions the spindle during asymmetric division. However, whether the role of LET-99 in cytokinesis is specific to asymmetric division and whether it acts through Gα to promote furrowing are unclear. Here we show that LET-99 contributes to furrowing in both asymmetrically and symmetrically dividing cells, independent of its function in spindle positioning and Gα regulation. LET-99 acts in a pathway parallel to anillin and is required for myosin enrichment into the contractile ring. These and other results suggest a positive feedback model in which LET-99 localizes to the presumptive cleavage furrow in response to the spindle and myosin. Once positioned there, LET-99 enhances myosin accumulation to promote furrowing in both symmetrically and asymmetrically dividing cells.

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A role for a novel centrosome cycle in asymmetric cell division

The Journal of Cell Biology ◽

10.1083/jcb.200612140 ◽

2007 ◽

Vol 177 (1) ◽

pp. 13-20 ◽

Cited By ~ 166

Author(s):

Nasser M. Rusan ◽

Mark Peifer

Keyword(s):

Asymmetric Cell Division ◽

Asymmetric Division ◽

Spindle Orientation ◽

The Novel ◽

Microtubule Organizing Center ◽

Spindle Positioning ◽

Central Brain ◽

Organizing Center ◽

Pericentriolar Material ◽

Step Mechanism

Tissue stem cells play a key role in tissue maintenance. Drosophila melanogaster central brain neuroblasts are excellent models for stem cell asymmetric division. Earlier work showed that their mitotic spindle orientation is established before spindle formation. We investigated the mechanism by which this occurs, revealing a novel centrosome cycle. In interphase, the two centrioles separate, but only one is active, retaining pericentriolar material and forming a “dominant centrosome.” This centrosome acts as a microtubule organizing center (MTOC) and remains stationary, forming one pole of the future spindle. The second centriole is inactive and moves to the opposite side of the cell before being activated as a centrosome/MTOC. This is accompanied by asymmetric localization of Polo kinase, a key centrosome regulator. Disruption of centrosomes disrupts the high fidelity of asymmetric division. We propose a two-step mechanism to ensure faithful spindle positioning: the novel centrosome cycle produces a single interphase MTOC, coarsely aligning the spindle, and spindle–cortex interactions refine this alignment.

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