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

Oxford Open Neuroscience, Год журнала: 2022, Номер 1

Опубликована: Янв. 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

Язык: Английский

Quiescent Neural Stem Cells for Brain Repair and Regeneration: Lessons from Model Systems DOI
Leo Otsuki, Andrea H. Brand

Trends in Neurosciences, Год журнала: 2020, Номер 43(4), С. 213 - 226

Опубликована: Март 9, 2020

Язык: Английский

Процитировано

58
Waking up quiescent neural stem cells: Molecular mechanisms and implications in neurodevelopmental disorders DOI Creative Commons
Wei Ding, Jiawen Huang, Hongyan Wang

и другие.

PLoS Genetics, Год журнала: 2020, Номер 16(4), С. e1008653 - e1008653

Опубликована: Апрель 23, 2020

Neural stem cells (NSCs) are crucial for development, regeneration, and repair of the nervous system. Most NSCs in mammalian adult brains quiescent, but response to extrinsic stimuli, they can exit from quiescence become reactivated give rise new neurons. The delicate balance between NSC activation is important neurogenesis maintenance. However, how transit remains largely elusive. Here, we discuss our current understanding molecular mechanisms underlying reactivation quiescent NSCs. We review recent advances on signaling pathways originated niche their crosstalk regulating reactivation. also highlight intrinsic paradigms that control Drosophila systems. emerging evidence modeling human neurodevelopmental disorders using

Язык: Английский

Процитировано

47
Golgi-dependent reactivation and regeneration of Drosophila quiescent neural stem cells DOI Creative Commons
Mahekta R. Gujar, Yang Gao, Xiang Teng

и другие.

Developmental Cell, Год журнала: 2023, Номер 58(19), С. 1933 - 1949.e5

Опубликована: Авг. 10, 2023

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, hallmark qNSCs. Here, we have found that qNSC protrusions can be regenerated upon injury. This regeneration process relies on the Golgi apparatus acts as major acentrosomal microtubule-organizing center in A Golgi-resident GTPase Arf1 its guanine nucleotide exchange factor Sec71 promote NSC 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 reactivation. Our findings established Drosophila qNSCs model identified Arf1/Sec71-Msps pathway growth

Язык: Английский

Процитировано

10
Histone lysine methyltransferase Pr‐set7/SETD8 promotes neural stem cell reactivation DOI Creative Commons
Jiawen Huang, Mahekta R. Gujar, Qiannan Deng

и другие.

EMBO Reports, Год журнала: 2021, Номер 22(4)

Опубликована: Фев. 10, 2021

The ability of neural stem cells (NSCs) to switch between quiescence and proliferation is crucial for brain development homeostasis. Increasing evidence suggests that variants histone lysine methyltransferases including KMT5A are associated with neurodevelopmental disorders. However, the function KMT5A/Pr-set7/SETD8 in central nervous system not well established. Here, we show Drosophila Pr-Set7 a novel regulator NSC reactivation. Loss pr-set7 causes delay reactivation loss H4K20 monomethylation brain. Through NSC-specific vivo profiling, demonstrate Pr-set7 binds promoter region cyclin-dependent kinase 1 (cdk1) Wnt pathway transcriptional co-activator earthbound1/jerky (ebd1). Further validation indicates required expression cdk1 ebd1 Similar Pr-set7, Cdk1 Ebd1 promote Finally, overexpression significantly suppressed defects observed pr-set7-depleted brains. Therefore, promotes by regulating signaling cell cycle progression. Our findings may contribute understanding mammalian KMT5A/PR-SET7/SETD8 during development.

Язык: Английский

Процитировано

21
Glial ferritin maintains neural stem cells via transporting iron required for self-renewal in Drosophila DOI Creative Commons
Zhixin Ma, Wenshu Wang, Xiaojing Yang

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Март 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 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.

Язык: Английский

Процитировано

3
Astrocytes control quiescent NSC reactivation via GPCR signaling–mediated F-actin remodeling DOI Creative Commons
Kun‐Yang Lin, Mahekta R. Gujar, Jiaen Lin

и другие.

Science Advances, Год журнала: 2024, Номер 10(30)

Опубликована: Июль 24, 2024

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.

Язык: Английский

Процитировано

3
Advances in the potential roles of Cullin-RING ligases in regulating autoimmune diseases DOI Creative Commons

Xiaoying Zhang,

Yue Liu, Tong Zhang

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Март 17, 2023

Cullin-RING ligases (CRLs) are the largest class of E3 ubiquitin regulating stability and subsequent activity a large number important proteins responsible for development progression various diseases, including autoimmune diseases (AIDs). However, detailed mechanisms pathogenesis AIDs complicated involve multiple signaling pathways. An in-depth understanding underlying regulatory initiation will aid in effective therapeutic strategies. CRLs play critical roles AIDs, partially by affecting key inflammation-associated pathways such as NF-κB, JAK/STAT, TGF-β. In this review, we summarize discuss potential inflammatory AIDs. Furthermore, advances novel strategies through targeting also highlighted.

Язык: Английский

Процитировано

7
Msps governs acentrosomal microtubule assembly and reactivation of quiescent neural stem cells DOI Creative Commons
Qiannan Deng,

Ye Sing Tan,

Liang Yuh Chew

и другие.

The EMBO Journal, Год журнала: 2021, Номер 40(19)

Опубликована: Авг. 9, 2021

The ability of stem cells to switch between quiescence and proliferation is crucial for tissue homeostasis regeneration. Drosophila quiescent neural (NSCs) extend a primary cellular protrusion from the cell body prior their reactivation. However, structure function this are not well established. Here, we show that in NSCs, microtubules predominantly acentrosomal oriented plus-end-out toward tip protrusion. We have identified Mini Spindles (Msps)/XMAP215 as key microtubule regulator NSCs governs NSC reactivation via regulating growth orientation. form membrane contact with neuropil E-cadherin, adhesion molecule, localizes these NSC-neuropil junctions. Msps plus-end directed motor protein Kinesin-2 promote cycle re-entry target E-cadherin during Together, work establishes organization Msps-Kinesin-2 pathway reactivation, part, by targeting E-cad sites.

Язык: Английский

Процитировано

15
Cereblon-Based Small-Molecule Compounds to Control Neural Stem Cell Proliferation in Regenerative Medicine DOI Creative Commons
Tomomi Sato, Takumi Ito, Hiroshi Handa

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 9

Опубликована: Март 11, 2021

Thalidomide, a sedative drug that was once excluded from the market owing to its teratogenic properties, later found be effective in treating multiple myeloma. We had previously demonstrated cereblon (CRBN) is target of thalidomide embryopathy and acts as substrate receptor for E3 ubiquitin ligase complex, Cullin-Ring 4 (CRL4CRBN) zebrafish chicks. CRBN originally identified gene responsible mild intellectual disability humans. Fetuses exposed early pregnancy were at risk neurodevelopmental disorders such autism, suggesting involved prenatal brain development. Recently, we controls proliferation neural stem cells developing brain, leading changes size. Our findings imply cell growth Accumulating evidence shows essential not only effects but also therapeutic thalidomide. This review summarizes recent progress research, focusing on effects. Investigation molecular mechanisms underlying derivatives, modulators (CELMoDs), reveals these provide ability recognize neosubstrates depending their structure. Understanding leads development novel technology called CRBN-based proteolysis-targeting chimeras (PROTACs) protein knockdown. These studies raise possibility small-molecule compounds regulating may developed application regenerative medicine.

Язык: Английский

Процитировано

13
Patronin/CAMSAP promotes reactivation and regeneration of Drosophila quiescent neural stem cells DOI Creative Commons
Mahekta R. Gujar, Yang Gao, Xiang Teng

и другие.

EMBO Reports, Год журнала: 2023, Номер 24(9)

Опубликована: Июль 13, 2023

The ability of stem cells to switch between quiescent and proliferative states is crucial for maintaining tissue homeostasis regeneration. Drosophila neural (qNSCs) extend a primary protrusion that enriched in acentrosomal microtubules can be regenerated upon injury. Arf1 promotes microtubule growth, reactivation (exit from quiescence), regeneration qNSC protrusions However, how regulated qNSCs remains elusive. Here, we show the minus-end binding protein Patronin/CAMSAP growth NSC reactivation. Patronin important localization at Golgi physically associates with Arf1, preferentially its GDP-bound form. also required protrusion, likely via regulation growth. Finally, functions upstream effector Msps/XMAP215 target cell adhesion molecule E-cadherin NSC-neuropil contact sites during Our findings reveal novel link A similar mechanism might apply various microtubule-dependent systems mammals.

Язык: Английский

Процитировано

5