scholarly journals PLP inhibits the activity of interphase centrosomes to ensure their proper segregation in stem cells

2013 ◽  
Vol 202 (7) ◽  
pp. 1013-1022 ◽  
Author(s):  
Dorothy A. Lerit ◽  
Nasser M. Rusan
Keyword(s):  
Stem Cells ◽  
Drosophila Melanogaster ◽  
Cell Division ◽  
Neural Stem Cells ◽  
Asymmetric Cell Division ◽  
Negative Regulator ◽  
Daughter Cells ◽  
Polo Kinase ◽  
Central Brain ◽  
Pericentriolar Material

Centrosomes determine the mitotic axis of asymmetrically dividing stem cells. Several studies have shown that the centrosomes of the Drosophila melanogaster central brain neural stem cells are themselves asymmetric, organizing varying levels of pericentriolar material and microtubules. This asymmetry produces one active and one inactive centrosome during interphase. We identify pericentrin-like protein (PLP) as a negative regulator of centrosome maturation and activity. We show that PLP is enriched on the inactive interphase centrosome, where it blocks recruitment of the master regulator of centrosome maturation, Polo kinase. Furthermore, we find that ectopic Centrobin expression influenced PLP levels on the basal centrosome, suggesting it may normally function to regulate PLP. Finally, we conclude that, although asymmetric centrosome maturation is not required for asymmetric cell division, it is required for proper centrosome segregation to the two daughter cells.

scholarly journals Understanding microcephaly through the study of centrosome regulation in Drosophila neural stem cells

2020 ◽  
Vol 48 (5) ◽  
pp. 2101-2115
Author(s):  
Beverly V. Robinson ◽  
Victor Faundez ◽  
Dorothy A. Lerit
Keyword(s):  
Stem Cells ◽  
Drosophila Melanogaster ◽  
Cell Division ◽  
Virus Infection ◽  
Neural Stem Cells ◽  
Head Circumference ◽  
Zika Virus ◽  
Asymmetric Cell Division ◽  
Significant Proportion ◽  
Neuronal Progenitors

Microcephaly is a rare, yet devastating, neurodevelopmental condition caused by genetic or environmental insults, such as the Zika virus infection. Microcephaly manifests with a severely reduced head circumference. Among the known heritable microcephaly genes, a significant proportion are annotated with centrosome-related ontologies. Centrosomes are microtubule-organizing centers, and they play fundamental roles in the proliferation of the neuronal progenitors, the neural stem cells (NSCs), which undergo repeated rounds of asymmetric cell division to drive neurogenesis and brain development. Many of the genes, pathways, and developmental paradigms that dictate NSC development in humans are conserved in Drosophila melanogaster. As such, studies of Drosophila NSCs lend invaluable insights into centrosome function within NSCs and help inform the pathophysiology of human microcephaly. This mini-review will briefly survey causative links between deregulated centrosome functions and microcephaly with particular emphasis on insights learned from Drosophila NSCs.

scholarly journals Phase Separation and Mechanical Forces in Regulating Asymmetric Cell Division of Neural Stem Cells

2021 ◽  
Vol 22 (19) ◽  
pp. 10267
Author(s):  
Yiqing Zhang ◽  
Heyang Wei ◽  
Wenyu Wen
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Phase Separation ◽  
Cell Division ◽  
Neural Stem Cells ◽  
Asymmetric Cell Division ◽  
Stem Cell Population ◽  
Mechanical Forces ◽  
Major Mechanism ◽  
Asymmetrically Distributed

Asymmetric cell division (ACD) of neural stem cells and progenitors not only renews the stem cell population but also ensures the normal development of the nervous system, producing various types of neurons with different shapes and functions in the brain. One major mechanism to achieve ACD is the asymmetric localization and uneven segregation of intracellular proteins and organelles into sibling cells. Recent studies have demonstrated that liquid-liquid phase separation (LLPS) provides a potential mechanism for the formation of membrane-less biomolecular condensates that are asymmetrically distributed on limited membrane regions. Moreover, mechanical forces have emerged as pivotal regulators of asymmetric neural stem cell division by generating sibling cell size asymmetry. In this review, we will summarize recent discoveries of ACD mechanisms driven by LLPS and mechanical forces.

scholarly journals Synthetic pluripotent bacterial stem cells

2018 ◽  
Author(s):  
Sara Molinari ◽  
David L. Shis ◽  
James Chappell ◽  
Oleg A. Igoshin ◽  
Matthew R. Bennett
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Plasmid Dna ◽  
Daughter Cell ◽  
Asymmetric Cell Division ◽  
Genetic Circuit ◽  
Pluripotent Cells ◽  
Daughter Cells ◽  
Asymmetric Partitioning ◽  
Asymmetrical Cell Division

AbstractA defining property of stem cells is their ability to differentiate via asymmetric cell division, in which a stem cell creates a differentiated daughter cell but retains its own phenotype. Here, we describe a synthetic genetic circuit for controlling asymmetrical cell division in Escherichia coli. Specifically, we engineered an inducible system that can bind and segregate plasmid DNA to a single position in the cell. Upon division, the co-localized plasmids are kept by one and only one of the daughter cells. The other daughter cell receives no plasmid DNA and is hence irreversibly differentiated from its sibling. In this way, we achieved asymmetric cell division though asymmetric plasmid partitioning. We also characterized an orthogonal inducible circuit that enables the simultaneous asymmetric partitioning of two plasmid species – resulting in pluripotent cells that have four distinct differentiated states. These results point the way towards engineering multicellular systems from prokaryotic hosts.

scholarly journals A circuit of protein-protein regulatory interactions enables polarity establishment in a bacterium

2018 ◽  
Author(s):  
Wei Zhao ◽  
Samuel W. Duvall ◽  
Kimberly A. Kowallis ◽  
Dylan T. Tomares ◽  
Haley N. Petitjean ◽  
...  
Keyword(s):  
Cell Division ◽  
Asymmetric Cell Division ◽  
Caulobacter Crescentus ◽  
Scaffold Protein ◽  
Cell Polarization ◽  
Negative Regulator ◽  
Scaffolding Proteins ◽  
Negative Bacterium ◽  
Regulatory Interactions ◽  
Daughter Cells

AbstractAsymmetric cell division generates specialized daughter cells that play a variety of roles including tissue morphogenesis in eukaryotes and pathogenesis in bacteria. In the gram-negative bacteriumCaulobacter crescentus, asymmetric localization of two biochemically distinct signaling hubs at opposite cell poles provides the foundation for asymmetric cell division. Through a set of genetic, synthetic biology and biochemical approaches we have characterized the regulatory interactions between three scaffolding proteins. These studies have revealed that the scaffold protein PodJ functions as a central mediator for organizing the new cell signaling hub, including promoting bipolarization of the central developmental scaffold protein PopZ. In addition, we identified that the old pole scaffold SpmX serves as a negative regulator of PodJ subcellular accumulation. These two scaffold-scaffold regulatory interactions serve as the core of an integrated cell polarization circuit that is layered on top of the cell-cycle circuitry to coordinate cell differentiation and asymmetric cell division.

scholarly journals Asymmetric cell division of mammary stem cells

Cell Division ◽  
2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shaan N. Chhabra ◽  
Brian W. Booth
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Asymmetric Cell Division ◽  
Mammary Stem Cells ◽  
Self Renewal ◽  
Symmetric Division ◽  
Daughter Cells ◽  
Mammary Stem

AbstractSomatic stem cells are distinguished by their capacity to regenerate themselves and also to produce daughter cells that will differentiate. Self-renewal is achieved through the process of asymmetric cell division which helps to sustain tissue morphogenesis as well as maintain homeostasis. Asymmetric cell division results in the development of two daughter cells with different fates after a single mitosis. Only one daughter cell maintains “stemness” while the other differentiates and achieves a non-stem cell fate. Stem cells also have the capacity to undergo symmetric division of cells that results in the development of two daughter cells which are identical. Symmetric division results in the expansion of the stem cell population. Imbalances and deregulations in these processes can result in diseases such as cancer. Adult mammary stem cells (MaSCs) are a group of cells that play a critical role in the expansion of the mammary gland during puberty and any subsequent pregnancies. Furthermore, given the relatively long lifespans and their capability to undergo self-renewal, adult stem cells have been suggested as ideal candidates for transformation events that lead to the development of cancer. With the possibility that MaSCs can act as the source cells for distinct breast cancer types; understanding their regulation is an important field of research. In this review, we discuss asymmetric cell division in breast/mammary stem cells and implications on further research. We focus on the background history of asymmetric cell division, asymmetric cell division monitoring techniques, identified molecular mechanisms of asymmetric stem cell division, and the role asymmetric cell division may play in breast cancer.

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