RT Journal Article
SR Electronic
T1 Asymmetric chromatin capture and nuclear envelopes separate endogenous and ectopic chromosomes after induced cell fusion
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.17.423124
DO 10.1101/2020.12.17.423124
A1 Bharath Sunchu
A1 Nicole Lee
A1 Roberto Carlos Segura
A1 Clemens Cabernard
YR 2020
UL http://biorxiv.org/content/early/2020/12/17/2020.12.17.423124.abstract
AB Metazoan cells accurately attach to, congress and segregate chromosomes during mitosis Additionally, hybrid cells derived through fertilization or somatic cell fusion also employ mechanisms to recognize and separate chromosomes of different origin. The underlying mechanisms are mostly unknown but could prevent aneuploidy and tumor formation. Here, we acutely induce fusion between Drosophila neural stem cells (neuroblasts) and differentiating ganglion mother cells (GMCs) in vivo to define how epigenetically distinct chromatin is recognized and segregated. We find that Nb-GMC hybrid cells align both endogenous (neuroblast-origin) and ectopic (GMC-origin) chromosomes at the metaphase plate through centrosome derived dual spindles. Mixing of endogenous and ectopic chromatin is prevented through an asymmetric, microtubule-dependent chromatin capture mechanism during interphase and physical boundaries imposed by nuclear envelopes. Although hybrid cells fail to accurately segregate ectopic chromatin, manifested in lagging chromosomes and chromosome bridges, transplanted brain tissue containing hybrid cells neither reduce the lifespan nor form visible tumors in host flies. We conclude that fly neural stem cells utilize asymmetric centrosome activity in interphase to capture and physically separate epigenetically distinct chromatin in a microtubule-dependent manner. We propose a novel chromosome recognition and separation mechanism that could also inform biased chromatid segregation observed in flies and vertebrates.Competing Interest StatementThe authors have declared no competing interest.