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

ABSTRACT: Controlling the orientation of cell division is important in the context of cell fate choices and tissue morphogenesis. However, the mechanisms providing the required positional information remain incompletely understood. Here we use stem cells of the Drosophila larval brain that stably maintain their axis of polarity and division between cell cycles to identify cues that orient cell division. Using live cell imaging of cultured brains, laser ablation and genetics, we reveal that division axis maintenance relies on their last-born daughter cell. We propose that, in addition to known intrinsic cues, stem cells in the developing fly brain are polarized by an extrinsic signal. We further find that division axis maintenance allows neuroblasts to maximize their contact area with glial cells known to provide protective and proliferative signals to neuroblasts.

SUBMITTER: Loyer N

PROVIDER: S-EPMC6138640 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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

Loyer Nicolas N Januschke Jens J

Nature communications 20180914 1

Controlling the orientation of cell division is important in the context of cell fate choices and tissue morphogenesis. However, the mechanisms providing the required positional information remain incompletely understood. Here we use stem cells of the Drosophila larval brain that stably maintain their axis of polarity and division between cell cycles to identify cues that orient cell division. Using live cell imaging of cultured brains, laser ablation and genetics, we reveal that division axis m ...[more]

PMID: 30218051

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Project description:As the microenvironment of a cell changes, associated mechanical cues may lead to changes in biochemical signaling and inherently mechanical processes such as mitosis. Here we explore the effects of confined mechanical environments on cellular responses during mitosis. Previously, effects of mechanical confinement have been difficult to optically observe in three-dimensional and in vivo systems. To address this challenge, we present a novel microfluidic perfusion culture system that allows controllable variation in the level of confinement in a single axis allowing observation of cell growth and division at the single-cell level. The device is capable of creating precise confinement conditions in the vertical direction varying from high (3 µm) to low (7 µm) confinement while also varying the substrate stiffness (E = 130 kPa and 1 MPa). The Human cervical carcinoma (HeLa) model with a known 3N+ karyotype was used for this study. For this cell line, we observe that mechanically confined cell cycles resulted in stressed cell divisions: (i) delayed mitosis, (ii) multi- daughter mitosis events (from 3 up to 5 daughter cells), (iii) unevenly sized daughter cells, and (iv) induction of cell death. In the highest confined conditions, the frequency of divisions producing more than two progeny was increased an astounding 50-fold from unconfined environments, representing about one half of all successful mitotic events. Notably, the majority of daughter cells resulting from multipolar divisions were viable after cytokinesis and, perhaps suggesting another regulatory checkpoint in the cell cycle, were in some cases observed to re-fuse with neighboring cells post-cytokinesis. The higher instances of abnormal mitosis that we report in confined mechanically stiff spaces, may lead to increased rates of abnormal, viable, cells in the population. This work provides support to a hypothesis that environmental mechanical cues influences structural mechanisms of mitosis such as geometric orientation of the mitotic plane or planes.

Dataset Information

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

Publications

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

Similar Datasets

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