Mitotic Implantation of the Transcription Factor Prospero via Phase Separation Drives Terminal Neuronal Differentiation

Liu, Xiaodan; Shen, Jingwen; Xie, Leiming; Wei, Zelin; Wong, Chouin; Li, Yiyao; Zheng, Xinhe; Li, Pilong; Song, Yan

doi:10.1016/j.devcel.2019.11.019

Cited by 70 publications

(65 citation statements)

References 74 publications

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“…Surprisingly, the relocation of CENP-E from the kinetochore to the central spindle is regulated by BubR1 phosphorylation ( Figure 2B) (74). Mechanistically, CENP-E contains an N-terminal motor domain followed by a long stretch of highly disordered region with a property to form biomolecular condensates via multivalent interactions with PRC1, CLASP, and other proteins (75). Correlative single-molecule electron microscopic analyses and in vivo real-time studies suggest that CENP-E exhibits structural changes elicited by BubR1 phosphorylation, which drives the formation of biomolecular condensates at the metaphase-anaphase transition ( Figure 2C) (74,76).…”

Section: Kinetochore Plasticity Reorganization and Llpsmentioning

confidence: 99%

Phase separation drives decision making in cell division

Liu

Wang

et al. 2020

Journal of Biological Chemistry

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Liquid-liquid phase separation (LLPS) of biomolecules drives the formation of subcellular compartments with distinct physicochemical properties. These compartments, free of lipid bilayers and therefore called membraneless organelles, include nucleoli, centrosomes, heterochromatin, and centromeres. These have emerged as a new paradigm to account for subcellular organization and cell fate decisions. Here we summarize recent studies linking LLPS to mitotic spindle, heterochromatin, and centromere assembly and their plasticity controls in the context of the cell division cycle, highlighting a functional role for phase behavior and material properties of proteins assembled onto heterochromatin, centromeres, and central spindles via LLPS. The techniques and tools for visualizing and harnessing membraneless organelle dynamics and plasticity in mitosis are also discussed, as is the potential for these discoveries to promote new research directions for investigating chromosome dynamics, plasticity, and inter-chromosome interactions in the decision-making process during mitosis.

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Section: Kinetochore Plasticity Reorganization and Llpsmentioning

confidence: 99%

Phase separation drives decision making in cell division

Liu

Wang

et al. 2020

Journal of Biological Chemistry

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“…Other TFs reported to repress NSC markers are Pros (Vaessin et al 1991, Choksi et al 2006, Cabernard and Doe 2009, Southall and Brand 2009, Colonques et al 2011, Liu et al 2020, LolaN (Flybase: Lola-PP) (Southall et al 2014) and Nerfin1 (Froldi et al 2015, Vissers et al 2018 in Type I lineages and Erm in Type II INPs (Weng et al 2010, Janssens et al 2014). All four, like Zfh1, show mutually repressive relationships with the Hes factors: they have strong Dpn binding in their vicinity (Figure 4) and most are downregulated in N/Hes tumours ( Figure 3A, although pros downregulation was less than the 1.8x cutoff we imposed).…”

Section: Discussionmentioning

confidence: 99%

Dissecting Hes-centered transcriptional networks in neural stem cell maintenance and tumorigenesis inDrosophila

Magadi

Voutyraki

Anagnostopoulos

et al. 2020

Preprint

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Neural stem cells divide during embryogenesis and post embryonic development to generate the entire complement of neurons and glia in the nervous system of vertebrates and invertebrates. Studies of the mechanisms controlling the fine balance between neural stem cells and more differentiated progenitors have shown that in every asymmetric cell division progenitors send a Delta-Notch signal back to their sibling stem cells. Here we show that excessive activation of Notch or overexpression of its direct targets of the Hes family causes stem-cell hyperplasias in the Drosophila larval central nervous system, which can progress to malignant tumours after allografting to adult hosts. We combined transcriptomic data from these hyperplasias with chromatin occupancy data for Dpn, a Hes transcription factor, to identify genes regulated by Hes factors in this process. We show that the Notch/Hes axis represses a cohort of transcription factor genes. These are excluded from the stem cells and promote early differentiation steps, most likely by preventing the reversion of immature progenitors to a stem-cell fate. Our results suggest that Notch signalling sets up a network of mutually repressing stemness and anti-stemness transcription factors, which include Hes proteins and Zfh1, respectively. This mutual repression ensures robust transition to neuronal and glial differentiation and its perturbation can lead to malignant transformation.

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“…The central spindle is a complex structure, containing several proteins including Borealin that have a microtubule binding domain that may allow the CPC to sense its environment (Trivedi et al, 2019b). Several central spindle components have been suggested to form structures by phase separation (So et al, 2019), including HP1 (Liu et al, 2020) and the CPC (Trivedi et al, 2019a). We suggest the central spindle forms a unique structure that allows for sensing bi-orientation of bivalents.…”

Section: Regulation Of Homolog Bi-orientation By the Cpcmentioning

confidence: 91%

Oocyte spindle assembly depends on multiple interactions between HP1 and the CPC

Wang

Defosse

Jang

et al. 2020

Preprint

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The chromosomes in the oocytes of many animals appear to promote bipolar spindle assembly. In Drosophila oocytes, spindle assembly requires the chromosomal passenger complex (CPC), which consists of INCENP, Borealin, Survivin and Aurora B. To determine what recruits the CPC to the chromosomes and its role in spindle assembly, we developed a strategy to manipulate the function and localization of INCENP, which is critical for recruiting the Aurora B kinase. We found that an interaction between Borealin and HP1 is crucial for the initial recruitment of the CPC to the chromosomes and is sufficient to build kinetochores and recruit spindle microtubules. We also found that HP1 moves from the chromosomes to the spindle microtubules along with the CPC, and based on this, propose a mechanism for how the CPC moves from the chromosomes to the microtubules. Within the central spindle, rather than at the centromeres, the CPC and HP1 are required for homologous chromosome bi-orientation.

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Mitotic Implantation of the Transcription Factor Prospero via Phase Separation Drives Terminal Neuronal Differentiation

Cited by 70 publications

References 74 publications

Phase separation drives decision making in cell division

Phase separation drives decision making in cell division

Dissecting Hes-centered transcriptional networks in neural stem cell maintenance and tumorigenesis inDrosophila

Oocyte spindle assembly depends on multiple interactions between HP1 and the CPC

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