A fly’s eye view of quiescent neural stem cells DOI Creative Commons
Mahekta R. Gujar, Hongyan Wang

Oxford Open Neuroscience, Journal Year: 2022, Volume and Issue: 1

Published: Jan. 1, 2022

Abstract The balance between proliferation and quiescence of stem cells is crucial in maintaining tissue homeostasis. Neural (NSCs) the brain have ability to be reactivated from a reversible quiescent state generate new neurons. However, how NSCs transit reactivation remains largely elusive. Drosophila larval NSCs, also known as neuroblasts, emerged an excellent vivo model study molecular mechanisms underlying NSC reactivation. Here, we discuss our current understanding Drosophila. We review most recent advances on epigenetic regulations microtubule cytoskeleton their cross-talk with signaling pathways that are required regulating

Language: Английский

TAZ Represses the Neuronal Commitment of Neural Stem Cells DOI Creative Commons

Natalia Robledinos-Antón,

Maribel Escoll, Kun‐Liang Guan

et al.

Cells, Journal Year: 2020, Volume and Issue: 9(10), P. 2230 - 2230

Published: Oct. 2, 2020

The mechanisms involved in regulation of quiescence, proliferation, and reprogramming Neural Stem Progenitor Cells (NSPCs) the mammalian brain are still poorly defined. Here, we studied role transcriptional co-factor TAZ, regulated by WNT Hippo pathways, homeostasis NSPCs. We found that, murine neurogenic niches striatal subventricular zone dentate gyrus granular zone, TAZ is highly expressed NSPCs declines with ageing. Moreover, expression lost immature neurons both regions. To characterize mechanistically neuronal differentiation, used midbrain-derived NSPC line ReNcell VM to replicate a non-animal model factors influencing differentiation lineage. knock-down forced led increased reduced respectively. TEADs-knockdown indicated that these co-partners required for suppression commitment differentiation. Genetic manipulation TAZ/TEAD system showed its participation repression SOX2 proneuronal genes ASCL1, NEUROG2, NEUROD1, leading impediment neurogenesis. usually considered co-activator promoting stem cell but our study indicates an additional function as repressor

Language: Английский

Citations

11
SUMOylation of Warts kinase promotes neural stem cell reactivation DOI Creative Commons
Yang Gao,

Ye Sing Tan,

Jiaen Lin

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 17, 2024

Language: Английский

Citations

1
Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription DOI Creative Commons
Sherzod A. Tokamov, Ting Su,

Anne Ullyot

et al.

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Feb. 8, 2021

The Hippo (Hpo) pathway regulates tissue growth in many animals. Multiple upstream components promote Hpo activity, but the organization of these different inputs, degree crosstalk between them, and whether they are regulated a distinct manner is not well understood. Kibra (Kib) activates by recruiting core kinase cassette to apical cortex. Here, we show that downregulates Drosophila Kib levels independently Yorkie-mediated transcription. We find signaling complex formation promotes degradation via SCF Slimb -mediated ubiquitination, this effect requires Merlin, Salvador, Hpo, Warts, mechanism functions other activators. Moreover, appears patterned differences mechanical tension across wing. propose mediated cytoskeletal serves control Kib-driven activation ensure optimally scaled growth.

Language: Английский

Citations

8
Mitochondria-enriched protrusions are associated with brain and intestinal stem cells in Drosophila DOI Creative Commons
Sharyn A. Endow, Sara Miller, Phuong Thao Ly

et al.

Communications Biology, Journal Year: 2019, Volume and Issue: 2(1)

Published: Nov. 22, 2019

Abstract Brain stem cells stop dividing in late Drosophila embryos and begin again early larvae after feeding induces reactivation. Quiescent neural (qNSCs) display an unusual cytoplasmic protrusion that is no longer present reactivated NSCs. The protrusions join the qNSCs to neuropil, brain regions are thought maintain NSCs undifferentiated state, but function of not known. Here we show qNSC contain clustered mitochondria likely maintained position by slow forward-and-backward microtubule growth. Larvae treated with a microtubule-stabilizing drug bundled microtubules enhanced mitochondrial clustering NSCs, together reduced We further intestinal mitochondria-enriched protrusions. stem-cell differ from previously reported extensions forming stem-cell-to-niche bridges could potentially both silence genes sense signals cell niche.

Language: Английский

Citations

8
The CRL4 E3 ligase Mahjong/DCAF1 controls cell competition through the transcription factor Xrp1, independently of polarity genes DOI Open Access
Amit Kumar, Nicholas E. Baker

Development, Journal Year: 2022, Volume and Issue: 149(22)

Published: Oct. 24, 2022

Cell competition, the elimination of cells surrounded by more fit neighbors, is proposed to suppress tumorigenesis. Mahjong (Mahj), a ubiquitin E3 ligase substrate receptor, has been thought mediate competition mutated for lethal giant larvae (lgl), neoplastic tumor suppressor that defines apical-basal polarity epithelial cells. Here, we show Drosophila mahjong, but not lgl [l(2)gl], are competed because they express bZip-domain transcription factor Xrp1, already known eliminate heterozygous ribosomal protein gene mutations (Rp/+ cells). Xrp1 expression in mahj mutant results activation JNK signaling, autophagosome accumulation, eIF2α phosphorylation and lower translation, just as Rp/+ Cells damage DNA binding-protein 1 (ddb1; pic) or cullin 4 (cul4), which encode partners Mahj, also display Xrp1-dependent phenotypes, does knockdown proteasome subunits. Our data suggest new model mahj-mediated cell independent couples turnover.

Language: Английский

Citations

5
Glial ferritin maintains neural stem cells via transporting iron required for self-renewal in Drosophila DOI Open Access
Zhixin Ma, Wenshu Wang, Xiaojing Yang

et al.

Published: March 4, 2024

Stem cell niche is critical for regulating the behavior of stem cells. Drosophila neural cells (Neuroblasts, NBs) are encased by glial closely, but it still remains unclear whether can regulate self-renewal and differentiation NBs. Here we show that ferritin produced glia, cooperates with Zip13 to transport iron into NBs energy production, which essential proliferation The knockdown encoding genes causes shortage in NBs, leads low premature Moreover, level production affected status establishing a bicellular homeostasis. In this study, demonstrate indispensable maintain unveiling novel role NB during brain development.

Language: Английский

Citations

0
Astrocytes control quiescent NSC reactivation via GPCR signaling-mediated F-actin remodeling DOI Open Access
Kun‐Yang Lin, Mahekta R. Gujar, Jiaen Lin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 13, 2024

Abstract The transitioning of neural stem cells (NSCs) between quiescent and proliferative states is fundamental for brain development homeostasis. Defects in NSC reactivation are associated with neurodevelopmental disorders. Drosophila NSCs extend an actin-rich primary protrusion toward the neuropil. However, function actin cytoskeleton during unknown. Here, we reveal fine F-actin structures protrusions by expansion super-resolution microscopy. We show that polymerization promotes nuclear translocation Mrtf, a microcephaly-associated transcription factor, development. regulated signaling cascade composed G-protein-coupled receptor (GPCR) Smog, G-protein αq subunit, Rho1 GTPase, Diaphanous (Dia)/Formin reactivation. Further, astrocytes secrete Smog ligand Fog to regulate Gαq-Rho1-Dia-mediated Together, establish Smog-Gαq-Rho1 axis derived from astrocytes, niche, regulates Dia-mediated dynamics

Language: Английский

Citations

0
Glial ferritin maintains neural stem cells via transporting iron required for self-renewal in Drosophila DOI Open Access
Zhixin Ma, Wenshu Wang, Xiaojing Yang

et al.

Published: Aug. 9, 2024

Stem cell niche is critical for regulating the behavior of stem cells. Drosophila neural cells (Neuroblasts, NBs) are encased by glial closely, but it still remains unclear whether can regulate self-renewal and differentiation NBs. Here we show that ferritin produced glia, cooperates with Zip13 to transport iron into NBs energy production, which essential proliferation The knockdown encoding genes causes shortage in via downregulating aconitase activity NAD + level, leads low premature mediated Prospero entering nuclei. More importantly, a potential target tumor suppression. In addition, level production affected status NBs, establishing bicellular homeostasis. this study, demonstrate indispensable maintain unveiling novel role NB during brain development.

Language: Английский

Citations

0
Glial ferritin maintains neural stem cells via transporting iron required for self-renewal in Drosophila DOI Creative Commons
Zhixin Ma, Wenshu Wang, Xiaojing Yang

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Sept. 10, 2024

Stem cell niche is critical for regulating the behavior of stem cells. Drosophila neural cells (Neuroblasts, NBs) are encased by glial closely, but it still remains unclear whether can regulate self-renewal and differentiation NBs. Here, we show that ferritin produced glia, cooperates with Zip13 to transport iron into NBs energy production, which essential proliferation The knockdown encoding genes causes shortage in via downregulating aconitase activity NAD + level, leads low premature mediated Prospero entering nuclei. More importantly, a potential target tumor suppression. In addition, level production affected status NBs, establishing bicellular homeostasis. this study, demonstrate indispensable maintain unveiling novel role NB during brain development.

Language: Английский

Citations

0
Golgi-dependent Reactivation and Regeneration of Quiescent Neural Stem Cells DOI Creative Commons
Mahekta R. Gujar, Yang Gao, Xiang Teng

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Aug. 23, 2022

Summary The ability of stem cells to switch between quiescent and proliferative states is crucial for maintaining tissue homeostasis regeneration. In Drosophila , neural (qNSCs) extend a primary protrusion, which removed prior NSC reactivation. Here, we have unravelled that qNSC protrusions can be regenerated upon injury. This regeneration process relies on the Golgi apparatus acts as major acentrosomal microtubule-organizing centre in qNSCs. A Golgi-resident GTPase Arf1 its guanine-nucleotide exchange factor Sec71 promote reactivation via regulation microtubule growth. physically associates with new effector Mini Spindles (Msps)/XMAP215, polymerase. Finally, functions upstream Msps target cell-adhesion molecule E-cadherin NSC-neuropil contact sites during Our findings established qNSCs model identified novel Arf1/Sec71-Msps pathway growth

Language: Английский

Citations

2