scholarly journals Arl2- and Msps-dependent microtubule growth governs asymmetric division

2016 ◽  
Vol 212 (6) ◽  
pp. 661-676 ◽  
Author(s):  
Keng Chen ◽  
Chwee Tat Koe ◽  
Zhanyuan Benny Xing ◽  
Xiaolin Tian ◽  
Fabrizio Rossi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Polarity ◽  
Control Cell ◽  
Asymmetric Division ◽  
New Paradigm ◽  
Self Renewal ◽  
Tubulin Binding ◽  
Microtubule Growth ◽  
Adp Ribosylation Factor

Asymmetric division of neural stem cells is a fundamental strategy to balance their self-renewal and differentiation. It is long thought that microtubules are not essential for cell polarity in asymmetrically dividing Drosophila melanogaster neuroblasts (NBs; neural stem cells). Here, we show that Drosophila ADP ribosylation factor like-2 (Arl2) and Msps, a known microtubule-binding protein, control cell polarity and spindle orientation of NBs. Upon arl2 RNA intereference, Arl2-GDP expression, or arl2 deletions, microtubule abnormalities and asymmetric division defects were observed. Conversely, overactivation of Arl2 leads to microtubule overgrowth and depletion of NBs. Arl2 regulates microtubule growth and asymmetric division through localizing Msps to the centrosomes in NBs. Moreover, Arl2 regulates dynein function and in turn centrosomal localization of D-TACC and Msps. Arl2 physically associates with tubulin cofactors C, D, and E. Arl2 functions together with tubulin-binding cofactor D to control microtubule growth, Msps localization, and NB self-renewal. Therefore, Arl2- and Msps-dependent microtubule growth is a new paradigm regulating asymmetric division of neural stem cells.

scholarly journals Tumour Suppressor Parafibromin/Hyrax Governs Cell Polarity and Centrosome Assembly in Neural Stem Cells

2021 ◽  
Author(s):  
Qiannan Deng ◽  
Cheng Wang ◽  
Chwee Tat Koe ◽  
Jan Peter Heinen ◽  
Ye Sing Tan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Polarity ◽  
Tumour Suppressor ◽  
New Paradigm ◽  
Microtubule Organizing Center ◽  
Larval Brain ◽  
Centrosomal Protein ◽  
Tumour Formation ◽  
Organizing Center

Neural stem cells (NSCs) divide asymmetrically to balance their self-renewal and differentiation. The imbalance can lead to NSC overgrowth and tumour formation. The function of Parafibromin, a conserved tumour suppressor, in the nervous system is not established. Here, we demonstrate that Drosophila Parafibromin/Hyrax (Hyx) inhibits NSC overgrowth by governing the cell polarity. Hyx is essential for the apicobasal polarity by localizing both apical and basal proteins asymmetrically in NSCs. hyx loss results in the symmetric division of NSCs, leading to the formation of supernumerary NSCs in the larval brain. Human Parafibromin fully rescues NSC overgrowth and cell polarity defects in Drosophila hyx mutant brains. Hyx plays a novel role in maintaining interphase microtubule-organizing center and mitotic spindle formation in NSCs. Hyx is required for the proper localization of a key centrosomal protein Polo and microtubule-binding proteins Msps and D-TACC in dividing NSCs. This study discovers that Hyx has a brain tumour suppressor-like function and maintains NSC polarity by regulating centrosome function and microtubule growth. The new paradigm that Parafibromin orchestrates cell polarity and centrosomal assembly may be relevant to Parafibromin/HRPT2-associated cancers.

The Balance Between Self-Renewal and Differentiation of Human Neural Stem Cells Requires the Amyloid Precursor Protein

2021 ◽  
Author(s):  
Khadijeh Shabani ◽  
Julien Pigeon ◽  
Marwan Benaissa Touil Zariouh ◽  
Tengyuan Liu ◽  
Azadeh Saffarian ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Self Renewal ◽  
Human Neural Stem Cells

scholarly journals Sevoflurane decreases self-renewal capacity and causes c-Jun N-terminal kinase–mediated damage of rat fetal neural stem cells

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Zeyong Yang ◽  
Jingjing Lv ◽  
Xingxing Li ◽  
Qiong Meng ◽  
Qiling Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Self Renewal

scholarly journals Cytokine receptor-Eb1 interaction couples cell polarity and fate during asymmetric cell division

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Cuie Chen ◽  
Ryan Cummings ◽  
Aghapi Mordovanakis ◽  
Alan J Hunt ◽  
Michael Mayer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Cell Fate ◽  
Cell Polarity ◽  
Adult Stem Cells ◽  
Asymmetric Cell Division ◽  
Cytokine Receptor ◽  
Spindle Orientation ◽  
Germline Stem Cells ◽  
Self Renewal

Asymmetric stem cell division is a critical mechanism for balancing self-renewal and differentiation. Adult stem cells often orient their mitotic spindle to place one daughter inside the niche and the other outside of it to achieve asymmetric division. It remains unknown whether and how the niche may direct division orientation. Here we discover a novel and evolutionary conserved mechanism that couples cell polarity to cell fate. We show that the cytokine receptor homolog Dome, acting downstream of the niche-derived ligand Upd, directly binds to the microtubule-binding protein Eb1 to regulate spindle orientation in Drosophila male germline stem cells (GSCs). Dome’s role in spindle orientation is entirely separable from its known function in self-renewal mediated by the JAK-STAT pathway. We propose that integration of two functions (cell polarity and fate) in a single receptor is a key mechanism to ensure an asymmetric outcome following cell division.

scholarly journals BEND6 is a nuclear antagonist of Notch signaling during self-renewal of neural stem cells

Development ◽  
2013 ◽  
Vol 140 (9) ◽  
pp. 1892-1902 ◽  
Author(s):  
Q. Dai ◽  
C. Andreu-Agullo ◽  
R. Insolera ◽  
L. C. Wong ◽  
S.-H. Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Notch Signaling ◽  
Self Renewal
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