Drosophila glia cells missing gene determines glia vs. neuron cell fate by asymmetric segregation of mRNA at stem cell division

Asymmetric stem cell division is often accompanied by stereotypical inheritance of the mother and daughter centrosomes. However, it remains unknown whether and how stem cell centrosomes are uniquely regulated and how this regulation may contribute to stem cell fate. Here we identify Klp10A, a microtubule-depolymerizing kinesin of the kinesin-13 family, as the first protein enriched in the stem cell centrosome in Drosophila male germline stem cells (GSCs). Depletion of klp10A results in abnormal elongation of the mother centrosomes in GSCs, suggesting the existence of a stem cell-specific centrosome regulation program. Concomitant with mother centrosome elongation, GSCs form asymmetric spindle, wherein the elongated mother centrosome organizes considerably larger half spindle than the other. This leads to asymmetric cell size, yielding a smaller differentiating daughter cell. We propose that klp10A functions to counteract undesirable asymmetries that may result as a by-product of achieving asymmetries essential for successful stem cell divisions.

Download Full-text

Asymmetric assembly of centromeres epigenetically regulates stem cell fate

The Journal of Cell Biology ◽

10.1083/jcb.201910084 ◽

2020 ◽

Vol 219 (4) ◽

Cited By ~ 4

Author(s):

Anna Ada Dattoli ◽

Ben L. Carty ◽

Antje M. Kochendoerfer ◽

Conall Morgan ◽

Annie E. Walshe ◽

...

Keyword(s):

Stem Cell ◽

Cell Division ◽

Cell Fate ◽

Germline Stem Cells ◽

Differentiated Cells ◽

Oocyte Meiosis ◽

Assembly Factor ◽

Stem Cell Division ◽

Female Germline ◽

Centromere Assembly

Centromeres are epigenetically defined by CENP-A–containing chromatin and are essential for cell division. Previous studies suggest asymmetric inheritance of centromeric proteins upon stem cell division; however, the mechanism and implications of selective chromosome segregation remain unexplored. We show that Drosophila female germline stem cells (GSCs) and neuroblasts assemble centromeres after replication and before segregation. Specifically, CENP-A deposition is promoted by CYCLIN A, while excessive CENP-A deposition is prevented by CYCLIN B, through the HASPIN kinase. Furthermore, chromosomes inherited by GSCs incorporate more CENP-A, making stronger kinetochores that capture more spindle microtubules and bias segregation. Importantly, symmetric incorporation of CENP-A on sister chromatids via HASPIN knockdown or overexpression of CENP-A, either alone or together with its assembly factor CAL1, drives stem cell self-renewal. Finally, continued CENP-A assembly in differentiated cells is nonessential for egg development. Our work shows that centromere assembly epigenetically drives GSC maintenance and occurs before oocyte meiosis.

Download Full-text

Ankle2, A Target of Zika Virus, Controls Asymmetric Cell Division of Neuroblasts and Uncovers a Novel Microcephaly Pathway

10.1101/611384 ◽

2019 ◽

Author(s):

N. Link ◽

H. Chung ◽

A. Jolly ◽

M. Withers ◽

B. Tepe ◽

...

Keyword(s):

Stem Cell ◽

Cell Division ◽

Nuclear Envelope ◽

Cell Fate ◽

Zika Virus ◽

Asymmetric Cell Division ◽

Brain Size ◽

Stem Cell Division ◽

Fate Determinants ◽

Cell Fate Determinants

ABSTRACTNeuroblasts in flies divide asymmetrically by establishing polarity, distributing cell fate determinants asymmetrically, and positioning their spindle for cell division. The apical complex contains aPKC, Bazooka (Par3), and Par6, and its activity depends on L(2)gl. We show that Ankle2 interacts with L(2)gl and affects aPKC. Reducing Ankle2 levels disrupts ER and nuclear envelope morphology, releasing the kinase Ballchen/VRK1 into the cytosol. These defects are associated with reduced phosphorylation of aPKC, disruption of Par complex localization, and spindle alignment defects. Importantly, removal of one copy ofballchen/VRK1orl(2)glsuppresses the loss ofAnkle2and restores viability and brain size. The Zika virus NS4A protein interacts withDrosophilaAnkle2 and VRK1 in dividing neuroblasts. Human mutational studies implicate this neural cell division pathway in microcephaly and motor neuron disease. In summary, NS4A, ANKLE2, VRK1 and LLGL1 define a novel pathway that impinges on asymmetric determinants of neural stem cell division.

Download Full-text

Breaking symmetry: the asymmetries in epigenetic inheritance

The Biochemist ◽

10.1042/bio_2020_110 ◽

2021 ◽

Vol 43 (1) ◽

pp. 14-19

Author(s):

Emily Zion ◽

Xin Chen

Keyword(s):

Stem Cell ◽

Cell Division ◽

Cell Fate ◽

Genetic Information ◽

Asymmetric Cell Division ◽

Epigenetic Inheritance ◽

Multicellular Organism ◽

Epigenetic Information ◽

Distinct Cell ◽

Stem Cell Division

Symmetry and asymmetry are the fundamental aspects of life. Most cells within a multicellular organism contain the same genetic information, passed on from one originating cell, the zygote; however, these cells can take on a variety of different identities, with diverse appearances and functions. A fundamental question in biology ponders how cells containing identical DNA content can take on different cell identities. Epigenetic mechanisms could be the symmetry-breaking factor, as they are able to change the gene expression in cells without changing the DNA sequence. While the process of duplication and segregation of DNA during cell division has been well studied, it is less understood how the epigenetic information is established and inherited in the cells within a multicellular organism. Studies of asymmetric stem cell division, where a stem cell division gives rise to a self-renewed stem cell and a differentiating daughter cell, provide a model to study how epigenetic information is maintained or changed to produce daughter cells with identical genetic information but distinct cell fates. Here, we discuss the findings and ideas of how epigenetic information is maintained or changed during asymmetric cell division and the importance of this asymmetry in influencing cell fate.

Download Full-text