Limits...
Asymmetrically dividing Drosophila neuroblasts utilize two spatially and temporally independent cytokinesis pathways.

Roth M, Roubinet C, Iffländer N, Ferrand A, Cabernard C - Nat Commun (2015)

Bottom Line: In most metazoan cells, contractile ring placement is regulated by the mitotic spindle through the centralspindlin complex, and potentially also the chromosomal passenger complex (CPC).Drosophila neuroblasts, asymmetrically dividing neural stem cells, but also other cells utilize both spindle-dependent and spindle-independent cleavage furrow positioning pathways.However, the relative contribution of each pathway towards cytokinesis is currently unclear.

View Article: PubMed Central - PubMed

Affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel, Switzerland.

ABSTRACT
Precise cleavage furrow positioning is required for faithful chromosome segregation and cell fate determinant distribution. In most metazoan cells, contractile ring placement is regulated by the mitotic spindle through the centralspindlin complex, and potentially also the chromosomal passenger complex (CPC). Drosophila neuroblasts, asymmetrically dividing neural stem cells, but also other cells utilize both spindle-dependent and spindle-independent cleavage furrow positioning pathways. However, the relative contribution of each pathway towards cytokinesis is currently unclear. Here we report that in Drosophila neuroblasts, the mitotic spindle, but not polarity cues, controls the localization of the CPC component Survivin. We also show that Survivin and the mitotic spindle are required to stabilize the position of the cleavage furrow in late anaphase and to complete furrow constriction. These results support the model that two spatially and temporally separate pathways control different key aspects during asymmetric cell division, ensuring correct cell fate determinant segregation and neuroblast self-renewal.

No MeSH data available.


Related in: MedlinePlus

Model.(a) Schematic representation of Survivin’s (orange) dynamic redistribution during asymmetric cell division. By metaphase, the entire Survivin pool is associated with chromosomes and lines up at the metaphase plate. After anaphase onset, a fraction of this Survivin pool is loaded onto microtubules and redistributed to the central spindle as well as the forming furrow region, which is shifted towards the basal cortex. Microtubules decorated with Survivin (black lines), contact the cortex at the cleavage furrow, forming a Survivin ring (orange ring) just inside the Myosin-containing contractile ring (green ring). This Survivin ring lines up with the Survivin pool at the central spindle during late anaphase/telophase, and both pools contribute to the forming midbody. (b) Two pathways with distinct functions control the generation of physical and molecular asymmetry in Drosophila neuroblasts. (b) (1) The polarity-dependent pathway induces asymmetric Myosin localization via Pins and Dlg shortly after anaphase onset. The molecular composition of this pathway is not known. Asymmetric Myosin localization is required for basal cleavage furrow positioning. (c) The spindle-dependent pathway not only stabilizes the basal furrow position (2) but also controls cleavage furrow ingression and completion (3). The vertical dashed line indicates the polarity/division axis. Both pathways act spatially and temporally separate to generate a large, self-renewed neuroblast and a differentiating small GMC. The mitotic spindle is responsible to relocalize the CPC, which activates the centralspindlin complex (Pav/Tum). Whether the centralspindlin complex maintains Myosin constriction through Rho1 is unclear in this system. Other CPC targets could act redundantly to complete cytokinesis. Nb, neuroblast; GMC, ganglion mother cell.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4544045&req=5

f8: Model.(a) Schematic representation of Survivin’s (orange) dynamic redistribution during asymmetric cell division. By metaphase, the entire Survivin pool is associated with chromosomes and lines up at the metaphase plate. After anaphase onset, a fraction of this Survivin pool is loaded onto microtubules and redistributed to the central spindle as well as the forming furrow region, which is shifted towards the basal cortex. Microtubules decorated with Survivin (black lines), contact the cortex at the cleavage furrow, forming a Survivin ring (orange ring) just inside the Myosin-containing contractile ring (green ring). This Survivin ring lines up with the Survivin pool at the central spindle during late anaphase/telophase, and both pools contribute to the forming midbody. (b) Two pathways with distinct functions control the generation of physical and molecular asymmetry in Drosophila neuroblasts. (b) (1) The polarity-dependent pathway induces asymmetric Myosin localization via Pins and Dlg shortly after anaphase onset. The molecular composition of this pathway is not known. Asymmetric Myosin localization is required for basal cleavage furrow positioning. (c) The spindle-dependent pathway not only stabilizes the basal furrow position (2) but also controls cleavage furrow ingression and completion (3). The vertical dashed line indicates the polarity/division axis. Both pathways act spatially and temporally separate to generate a large, self-renewed neuroblast and a differentiating small GMC. The mitotic spindle is responsible to relocalize the CPC, which activates the centralspindlin complex (Pav/Tum). Whether the centralspindlin complex maintains Myosin constriction through Rho1 is unclear in this system. Other CPC targets could act redundantly to complete cytokinesis. Nb, neuroblast; GMC, ganglion mother cell.

Mentions: Taken together, the results reported here not only corroborate the recent finding that asymmetrically dividing neuroblasts contain two cytokinesis pathways11 but also that they are spatially and temporally separated. It is thus the timely interplay between the two pathways that ultimately ensures that the cleavage furrow is formed at the correct position. Our phenotypic characterization is inconsistent with the idea that the two pathways are simply acting redundantly and that the polarity-dependent pathway serves as a backup cytokinesis pathway. On the basis of earlier results and our findings here, we thus propose that Drosophila neuroblasts utilize the polarity-dependent pathway, composed of the polarity proteins Pins and Dlg, to induce asymmetric Myosin localization during early anaphase1115. The spindle-dependent pathway subsequently engages the CPC, but possibly also other molecules, to stabilize the position of the furrow in late anaphase/early telophase and to complete cytokinesis1115 (Fig. 8). In the future, it will be important to elucidate the mechanism by which the CPC and the mitotic spindle regulate accurate furrow positioning. Furthermore, the regulatory mechanisms ensuring the timely interplay between the polarity and spindle pathway remain to be investigated.


Asymmetrically dividing Drosophila neuroblasts utilize two spatially and temporally independent cytokinesis pathways.

Roth M, Roubinet C, Iffländer N, Ferrand A, Cabernard C - Nat Commun (2015)

Model.(a) Schematic representation of Survivin’s (orange) dynamic redistribution during asymmetric cell division. By metaphase, the entire Survivin pool is associated with chromosomes and lines up at the metaphase plate. After anaphase onset, a fraction of this Survivin pool is loaded onto microtubules and redistributed to the central spindle as well as the forming furrow region, which is shifted towards the basal cortex. Microtubules decorated with Survivin (black lines), contact the cortex at the cleavage furrow, forming a Survivin ring (orange ring) just inside the Myosin-containing contractile ring (green ring). This Survivin ring lines up with the Survivin pool at the central spindle during late anaphase/telophase, and both pools contribute to the forming midbody. (b) Two pathways with distinct functions control the generation of physical and molecular asymmetry in Drosophila neuroblasts. (b) (1) The polarity-dependent pathway induces asymmetric Myosin localization via Pins and Dlg shortly after anaphase onset. The molecular composition of this pathway is not known. Asymmetric Myosin localization is required for basal cleavage furrow positioning. (c) The spindle-dependent pathway not only stabilizes the basal furrow position (2) but also controls cleavage furrow ingression and completion (3). The vertical dashed line indicates the polarity/division axis. Both pathways act spatially and temporally separate to generate a large, self-renewed neuroblast and a differentiating small GMC. The mitotic spindle is responsible to relocalize the CPC, which activates the centralspindlin complex (Pav/Tum). Whether the centralspindlin complex maintains Myosin constriction through Rho1 is unclear in this system. Other CPC targets could act redundantly to complete cytokinesis. Nb, neuroblast; GMC, ganglion mother cell.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4544045&req=5

f8: Model.(a) Schematic representation of Survivin’s (orange) dynamic redistribution during asymmetric cell division. By metaphase, the entire Survivin pool is associated with chromosomes and lines up at the metaphase plate. After anaphase onset, a fraction of this Survivin pool is loaded onto microtubules and redistributed to the central spindle as well as the forming furrow region, which is shifted towards the basal cortex. Microtubules decorated with Survivin (black lines), contact the cortex at the cleavage furrow, forming a Survivin ring (orange ring) just inside the Myosin-containing contractile ring (green ring). This Survivin ring lines up with the Survivin pool at the central spindle during late anaphase/telophase, and both pools contribute to the forming midbody. (b) Two pathways with distinct functions control the generation of physical and molecular asymmetry in Drosophila neuroblasts. (b) (1) The polarity-dependent pathway induces asymmetric Myosin localization via Pins and Dlg shortly after anaphase onset. The molecular composition of this pathway is not known. Asymmetric Myosin localization is required for basal cleavage furrow positioning. (c) The spindle-dependent pathway not only stabilizes the basal furrow position (2) but also controls cleavage furrow ingression and completion (3). The vertical dashed line indicates the polarity/division axis. Both pathways act spatially and temporally separate to generate a large, self-renewed neuroblast and a differentiating small GMC. The mitotic spindle is responsible to relocalize the CPC, which activates the centralspindlin complex (Pav/Tum). Whether the centralspindlin complex maintains Myosin constriction through Rho1 is unclear in this system. Other CPC targets could act redundantly to complete cytokinesis. Nb, neuroblast; GMC, ganglion mother cell.
Mentions: Taken together, the results reported here not only corroborate the recent finding that asymmetrically dividing neuroblasts contain two cytokinesis pathways11 but also that they are spatially and temporally separated. It is thus the timely interplay between the two pathways that ultimately ensures that the cleavage furrow is formed at the correct position. Our phenotypic characterization is inconsistent with the idea that the two pathways are simply acting redundantly and that the polarity-dependent pathway serves as a backup cytokinesis pathway. On the basis of earlier results and our findings here, we thus propose that Drosophila neuroblasts utilize the polarity-dependent pathway, composed of the polarity proteins Pins and Dlg, to induce asymmetric Myosin localization during early anaphase1115. The spindle-dependent pathway subsequently engages the CPC, but possibly also other molecules, to stabilize the position of the furrow in late anaphase/early telophase and to complete cytokinesis1115 (Fig. 8). In the future, it will be important to elucidate the mechanism by which the CPC and the mitotic spindle regulate accurate furrow positioning. Furthermore, the regulatory mechanisms ensuring the timely interplay between the polarity and spindle pathway remain to be investigated.

Bottom Line: In most metazoan cells, contractile ring placement is regulated by the mitotic spindle through the centralspindlin complex, and potentially also the chromosomal passenger complex (CPC).Drosophila neuroblasts, asymmetrically dividing neural stem cells, but also other cells utilize both spindle-dependent and spindle-independent cleavage furrow positioning pathways.However, the relative contribution of each pathway towards cytokinesis is currently unclear.

View Article: PubMed Central - PubMed

Affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50-70, CH-4056 Basel, Switzerland.

ABSTRACT
Precise cleavage furrow positioning is required for faithful chromosome segregation and cell fate determinant distribution. In most metazoan cells, contractile ring placement is regulated by the mitotic spindle through the centralspindlin complex, and potentially also the chromosomal passenger complex (CPC). Drosophila neuroblasts, asymmetrically dividing neural stem cells, but also other cells utilize both spindle-dependent and spindle-independent cleavage furrow positioning pathways. However, the relative contribution of each pathway towards cytokinesis is currently unclear. Here we report that in Drosophila neuroblasts, the mitotic spindle, but not polarity cues, controls the localization of the CPC component Survivin. We also show that Survivin and the mitotic spindle are required to stabilize the position of the cleavage furrow in late anaphase and to complete furrow constriction. These results support the model that two spatially and temporally separate pathways control different key aspects during asymmetric cell division, ensuring correct cell fate determinant segregation and neuroblast self-renewal.

No MeSH data available.


Related in: MedlinePlus