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Article: NEKL-4 regulates microtubule stability and mitochondrial health in

Power, Kaiden M / Nguyen, Ken C / Silva, Andriele / Singh, Shaneen / Hall, David H / Rongo, Christopher / Barr, Maureen M

bioRxiv : the preprint server for biology

2024

Abstract: Ciliopathies are often caused by defects in the ciliary microtubule core. Glutamylation is abundant in cilia, and its dysregulation may contribute to ciliopathies and neurodegeneration. Mutation of the deglutamylase CCP1 causes infantile-onset ... ...

Abstract	Ciliopathies are often caused by defects in the ciliary microtubule core. Glutamylation is abundant in cilia, and its dysregulation may contribute to ciliopathies and neurodegeneration. Mutation of the deglutamylase CCP1 causes infantile-onset neurodegeneration. In
Language	English
Publishing date	2024-02-14
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.14.580304
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Article ; Online: Transient Redirection of SVZ Stem Cells to Oligodendrogenesis by FGFR3 Activation Promotes Remyelination.

Kang, Wenfei / Nguyen, Ken C Q / Hébert, Jean M

Stem cell reports

2021 Volume 12, Issue 6, Page(s) 1223–1231

Abstract: Stimulating oligodendrocyte (OL) production from endogenous progenitor cells is an important strategy for myelin repair and functional restoration after disease or injury-induced demyelination. Subventricular zone (SVZ) stem cells are multipotential, ... ...

Abstract	Stimulating oligodendrocyte (OL) production from endogenous progenitor cells is an important strategy for myelin repair and functional restoration after disease or injury-induced demyelination. Subventricular zone (SVZ) stem cells are multipotential, generating neurons and oligodendroglia. The factors that regulate the fate of these stem cells are poorly defined. In this study, we show that genetically increasing fibroblast growth factor receptor-3 (FGFR3) activity in adult SVZ stem cells transiently and dramatically redirects their differentiation from the neuronal to the oligodendroglial lineage after pathological demyelination. The increased SVZ-derived oligodendrogenesis leads to improved OL regeneration and myelin repair, not only in the corpus callosum (a normal destination for SVZ-derived oligodendroglial cells), but also in the lower cortical layers. This study identifies FGF signaling as a potent target for improving endogenous SVZ-derived OL regeneration and remyelination.
MeSH term(s)	Adult Stem Cells/metabolism ; Adult Stem Cells/pathology ; Animals ; Corpus Callosum/metabolism ; Corpus Callosum/pathology ; Demyelinating Diseases/metabolism ; Demyelinating Diseases/pathology ; Lateral Ventricles/metabolism ; Lateral Ventricles/pathology ; Mice ; Myelin Sheath/physiology ; Neural Stem Cells/metabolism ; Neural Stem Cells/pathology ; Oligodendroglia/metabolism ; Oligodendroglia/pathology ; Receptor, Fibroblast Growth Factor, Type 3/genetics ; Receptor, Fibroblast Growth Factor, Type 3/metabolism ; Regeneration ; Signal Transduction
Chemical Substances	Fgfr3 protein, mouse (EC 2.7.10.1) ; Receptor, Fibroblast Growth Factor, Type 3 (EC 2.7.10.1)
Language	English
Publishing date	2021-01-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2720528-9
ISSN	2213-6711 ; 2213-6711
ISSN (online)	2213-6711
ISSN	2213-6711
DOI	10.1016/j.stemcr.2019.05.006
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Ciliary intrinsic mechanisms regulate dynamic ciliary extracellular vesicle release from sensory neurons.

Wang, Juan / Saul, Josh / Nikonorova, Inna A / Cruz, Carlos Nava / Power, Kaiden M / Nguyen, Ken C / Hall, David H / Barr, Maureen M

bioRxiv : the preprint server for biology

2023

Abstract: Cilia-derived extracellular vesicles (EVs) contain signaling proteins and act in intercellular communication. Polycystin-2 (PKD-2), a transient receptor potential channel, is a conserved ciliary EVs cargo. ...

Abstract	Cilia-derived extracellular vesicles (EVs) contain signaling proteins and act in intercellular communication. Polycystin-2 (PKD-2), a transient receptor potential channel, is a conserved ciliary EVs cargo.
Language	English
Publishing date	2023-11-03
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.01.565151
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Article ; Online: Comparative connectomics of dauer reveals developmental plasticity.

Yim, Hyunsoo / Choe, Daniel T / Bae, J Alexander / Choi, Myung-Kyu / Kang, Hae-Mook / Nguyen, Ken C Q / Ahn, Soungyub / Bahn, Sang-Kyu / Yang, Heeseung / Hall, David H / Kim, Jinseop S / Lee, Junho

Nature communications

2024 Volume 15, Issue 1, Page(s) 1546

Abstract: A fundamental question in neurodevelopmental biology is how flexibly the nervous system changes during development. To address this, we reconstructed the chemical connectome of dauer, an alternative developmental stage of nematodes with distinct ... ...

Abstract	A fundamental question in neurodevelopmental biology is how flexibly the nervous system changes during development. To address this, we reconstructed the chemical connectome of dauer, an alternative developmental stage of nematodes with distinct behavioral characteristics, by volumetric reconstruction and automated synapse detection using deep learning. With the basic architecture of the nervous system preserved, structural changes in neurons, large or small, were closely associated with connectivity changes, which in turn evoked dauer-specific behaviors such as nictation. Graph theoretical analyses revealed significant dauer-specific rewiring of sensory neuron connectivity and increased clustering within motor neurons in the dauer connectome. We suggest that the nervous system in the nematode has evolved to respond to harsh environments by developing a quantitatively and qualitatively differentiated connectome.
MeSH term(s)	Animals ; Caenorhabditis elegans/physiology ; Connectome ; Nematoda ; Synapses ; Motor Neurons
Language	English
Publishing date	2024-02-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45943-3
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Article ; Online: The initial expansion of the C. elegans syncytial germ line is coupled to incomplete primordial germ cell cytokinesis.

Bauer, Jack / Poupart, Vincent / Goupil, Eugénie / Nguyen, Ken C Q / Hall, David H / Labbé, Jean-Claude

Development (Cambridge, England)

2021 Volume 148, Issue 18

Abstract: The C. elegans germline is organized as a syncytium in which each germ cell possesses an intercellular bridge that is maintained by a stable actomyosin ring and connected to a common pool of cytoplasm, termed the rachis. How germ cells undergo ... ...

Abstract	The C. elegans germline is organized as a syncytium in which each germ cell possesses an intercellular bridge that is maintained by a stable actomyosin ring and connected to a common pool of cytoplasm, termed the rachis. How germ cells undergo cytokinesis while maintaining this syncytial architecture is not completely understood. Here, we use live imaging to characterize primordial germ cell (PGC) division in C. elegans first-stage larvae. We show that each PGC possesses a stable intercellular bridge that connects it to a common pool of cytoplasm, which we term the proto-rachis. We further show that the first PGC cytokinesis is incomplete and that the stabilized cytokinetic ring progressively moves towards the proto-rachis and eventually integrates with it. Our results support a model in which the initial expansion of the C. elegans syncytial germline occurs by incomplete cytokinesis, where one daughter germ cell inherits the actomyosin ring that was newly formed by stabilization of the cytokinetic ring, while the other inherits the pre-existing stable actomyosin ring. We propose that such a mechanism of iterative cytokinesis incompletion underpins C. elegans germline expansion and maintenance.
MeSH term(s)	Actin Cytoskeleton/physiology ; Actomyosin/physiology ; Animals ; Caenorhabditis elegans/cytology ; Cytokinesis/physiology ; Cytoplasm/physiology ; Germ Cells/cytology ; Giant Cells/physiology
Chemical Substances	Actomyosin (9013-26-7)
Language	English
Publishing date	2021-07-21
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.199633
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Article ; Online: Innexin function dictates the spatial relationship between distal somatic cells in the

Tolkin, Theadora / Mohammad, Ariz / Starich, Todd A / Nguyen, Ken C Q / Hall, David H / Schedl, Tim / Hubbard, E Jane Albert / Greenstein, David

eLife

2022 Volume 11

Abstract: Gap-junctional signaling mediates myriad cellular interactions in metazoans. Yet, how gap junctions control the positioning of cells in organs is not well understood. Innexins compose gap junctions in invertebrates and affect organ architecture. Here, we ...

Abstract	Gap-junctional signaling mediates myriad cellular interactions in metazoans. Yet, how gap junctions control the positioning of cells in organs is not well understood. Innexins compose gap junctions in invertebrates and affect organ architecture. Here, we investigate the roles of gap-junctions in controlling distal somatic gonad architecture and its relationship to underlying germline stem cells in
MeSH term(s)	Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Germ Cells/metabolism ; Gonads/metabolism ; Stem Cells/metabolism
Chemical Substances	Caenorhabditis elegans Proteins
Language	English
Publishing date	2022-09-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.74955
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Article ; Online: Correction: Kinesin-3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components.

Oliver, Devyn / Ramachandran, Shankar / Philbrook, Alison / Lambert, Christopher M / Nguyen, Ken C Q / Hall, David H / Francis, Michael M

PLoS genetics

2022 Volume 18, Issue 6, Page(s) e1010291

Abstract: This corrects the article DOI: 10.1371/journal.pgen.1010016.]. ...

Abstract	[This corrects the article DOI: 10.1371/journal.pgen.1010016.].
Language	English
Publishing date	2022-06-24
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1010291
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Article ; Online: Kinesin-3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components.

Oliver, Devyn / Ramachandran, Shankar / Philbrook, Alison / Lambert, Christopher M / Nguyen, Ken C Q / Hall, David H / Francis, Michael M

PLoS genetics

2022 Volume 18, Issue 1, Page(s) e1010016

Abstract: The functional properties of neural circuits are defined by the patterns of synaptic connections between their partnering neurons, but the mechanisms that stabilize circuit connectivity are poorly understood. We systemically examined this question at ... ...

Abstract	The functional properties of neural circuits are defined by the patterns of synaptic connections between their partnering neurons, but the mechanisms that stabilize circuit connectivity are poorly understood. We systemically examined this question at synapses onto newly characterized dendritic spines of C. elegans GABAergic motor neurons. We show that the presynaptic adhesion protein neurexin/NRX-1 is required for stabilization of postsynaptic structure. We find that early postsynaptic developmental events proceed without a strict requirement for synaptic activity and are not disrupted by deletion of neurexin/nrx-1. However, in the absence of presynaptic NRX-1, dendritic spines and receptor clusters become destabilized and collapse prior to adulthood. We demonstrate that NRX-1 delivery to presynaptic terminals is dependent on kinesin-3/UNC-104 and show that ongoing UNC-104 function is required for postsynaptic maintenance in mature animals. By defining the dynamics and temporal order of synapse formation and maintenance events in vivo, we describe a mechanism for stabilizing mature circuit connectivity through neurexin-based adhesion.
MeSH term(s)	Animals ; Axons/metabolism ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/metabolism ; Cell Adhesion Molecules, Neuronal/metabolism ; Dendritic Spines/metabolism ; Nerve Tissue Proteins/metabolism ; Presynaptic Terminals/metabolism
Chemical Substances	Caenorhabditis elegans Proteins ; Cell Adhesion Molecules, Neuronal ; Nerve Tissue Proteins ; UNC-104 protein, C elegans ; nrx-1 protein, C elegans
Language	English
Publishing date	2022-01-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1010016
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Article ; Online: Large vesicle extrusions from

Wang, Yu / Arnold, Meghan Lee / Smart, Anna Joelle / Wang, Guoqiang / Androwski, Rebecca J / Morera, Andres / Nguyen, Ken C Q / Schweinsberg, Peter J / Bai, Ge / Cooper, Jason / Hall, David H / Driscoll, Monica / Grant, Barth D

eLife

2023 Volume 12

Abstract: Caenorhabditis ... ...

Abstract	Caenorhabditis elegans
MeSH term(s)	Animals ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/metabolism ; Neurodegenerative Diseases/metabolism ; Apoptosis/physiology ; Phagocytosis/physiology ; Phagosomes/metabolism ; Neurons/metabolism ; Neuroglia/metabolism ; Carrier Proteins/metabolism ; GTP Phosphohydrolases/metabolism ; Mammals/metabolism
Chemical Substances	Caenorhabditis elegans Proteins ; Carrier Proteins ; GTP Phosphohydrolases (EC 3.6.1.-)
Language	English
Publishing date	2023-03-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.82227
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Article: Mechanical force of uterine occupation enables large vesicle extrusion from proteostressed maternal neurons.

Wang, Guoqiang / Guasp, Ryan / Salam, Sangeena / Chuang, Edward / Morera, Andrés / Smart, Anna J / Jimenez, David / Shekhar, Sahana / Melentijevic, Ilija / Nguyen, Ken C / Hall, David H / Grant, Barth D / Driscoll, Monica

bioRxiv : the preprint server for biology

2023

Abstract: Large vesicle extrusion from neurons may contribute to spreading pathogenic protein aggregates and promoting inflammatory responses, two mechanisms leading to neurodegenerative disease. Factors that regulate extrusion of large vesicles, such as exophers ... ...

Abstract	Large vesicle extrusion from neurons may contribute to spreading pathogenic protein aggregates and promoting inflammatory responses, two mechanisms leading to neurodegenerative disease. Factors that regulate extrusion of large vesicles, such as exophers produced by proteostressed
Language	English
Publishing date	2023-11-16
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.13.565361
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