Neogenin-YAP signaling in neocortical astrocytic differentiation

Huang, Zhihui; Xiong, Wen-Cheng

doi:10.1080/23262133.2016.1248735

Cited by 12 publications

(11 citation statements)

References 52 publications

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“…NEO1 is expressed in multiple types of brain cells, including astrocytes (15), NSCs (25), and neurons (26). Neo GFAP-Cre mice are likely to abolish its expression in all these cell types (27).…”

Section: Similar Vessel Deficit In Astrocyte But Not Pyramidal Neuromentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Neogenin (NEO1), a DCC family receptor for netrins (14), is abundantly expressed in astrocytes, in addition to neural stem cells (NSCs), oligodendrocytes, and neurons in the brain (15). Although NEO1 is initially identified as a NTN1 receptor, its role in NTN1 regulated axonal guidance remains un-identified (15,16). NEO1 hypomorphic allele exhibits multiple phenotypes, including early neonatal death, neonatal hydrocephalus (17), and olfactory neuron migration deficit (18).…”

Section: Introductionmentioning

confidence: 99%

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Astrocytic neogenin/netrin-1 pathway promotes blood vessel homeostasis and function in mouse cortex

Yao¹,

Hu²,

Li³

et al. 2020

Journal of Clinical Investigation

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Astrocytes play multiple functions in the brain, including blood vessel (BV) homeostasis and function. However, the underlying mechanisms remain elusive. Here, we provide evidence for astrocytic neogenin (NEO1), a member of deleted in colorectal cancer (DCC) family netrin receptors, to be involved in this event. Mice with Neo1 depletion in astrocytes exhibited clustered astrocyte distribution and increased BVs in their cortex. These BVs were leaky with reduced blood flow, disrupted basement membranes (vBMs), decreased pericytes, impaired endothelial cell (EC) barrier, and elevated tip EC proliferation. Increased proliferation was also detected in cultured ECs exposed to the conditional medium (CM) of NEO1 depleted astrocytes. Further screening for angiogenetic factors in the CM identifies netrin-1 (NTN1), whose expression was decreased in NEO1 depleted cortical astrocytes. Adding NTN1 into the CM of NEO1 depleted astrocytes attenuated EC proliferation. Expressing NTN1 in NEO1 mutant cortical astrocytes ameliorated phenotypes in blood-brain barrier (BBB), EC, and astrocyte distribution. NTN1 depletion in astrocytes resulted in similar BV/BBB deficits in the cortex as those of Neo1 mutant mice. In aggregates, these results uncovered an unrecognized pathway, astrocytic NEO1 to NTN1, not only regulating astrocyte distribution, but also promoting cortical BV homeostasis and function.

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Section: Similar Vessel Deficit In Astrocyte But Not Pyramidal Neuromentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Astrocytic neogenin/netrin-1 pathway promotes blood vessel homeostasis and function in mouse cortex

Yao¹,

Hu²,

Li³

et al. 2020

Journal of Clinical Investigation

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“…YAP can be sequestered at cellular adherens and tight junctions, thereby suppressing its transcriptional activity as a mechanism for cellular contact inhibition [32,33]. YAP signaling has been implicated in astrogliogenesis and astrocytic differentiation in the developing neocortex [34,35]. Indeed, YAP knockout mice develop reactive astrogliosis in the cortex supporting its critical involvement in brain development [36].…”

Section: Introductionmentioning

confidence: 99%

A connexin43/YAP axis regulates astroglial-mesenchymal transition in hemoglobin induced astrocyte activation

et al. 2018

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Reactive astrogliosis is a common response to insults to the central nervous system, but the mechanism remains unknown. In this study, we found the temporal and spatial differential expression of glial fibrillary acidic protein (GFAP) and Vimentin in the intracerebral hemorrhage (ICH) mouse brain, indicating that the de-differentiation and astroglial-mesenchymal transition (AMT) of astrocytes might be an early event in reactive astrogliosis. Further we verified the AMT finding in purified astrocyte cultures exposed to hemoglobin (Hb). Additionally, Connexin 43 (Cx43) downregulation and YAP nuclear translocation were observed in Hb-activated astrocytes. Knocking down Cx43 by siRNA triggered YAP nuclear translocation. Cx43 and YAP were physically associated as determined by immunofluorescence and co-immunoprecipitation. We propose that astrocytes undergo AMT during Hb-induced activation where Cx43 downregulation facilitates YAP nuclear translocation is a novel mechanism involved in this process. Cx43-YAP interaction may represent a potential therapeutic target for modulating astrocyte activation.

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“…The mechanisms regulating neuronal stem cells (NSCs) populations are very complicated, and crucial roles are played by many signaling pathways in regulating NSCs proliferation, and include Notch1 [ 4 ], BMP [ 5 ], Shh [ 6 ], EGFR [ 4 , 7 ] and Wnt signaling pathways [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic deletion of Rnd3 in neural stem cells promotes proliferation via upregulation of Notch signaling

Dong

Lin

et al. 2017

Oncotarget

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Rnd3, a Rho GTPase, is involved in the inhibition of actin cytoskeleton dynamics through the Rho kinase-dependent signaling pathway. We previously demonstrated that mice with genetic deletion of Rnd3 developed a markedly larger brain compared with wild-type mice. Here, we demonstrate that Rnd3 knockout mice developed an enlarged subventricular zone, and we identify a novel role for Rnd3 as an inhibitor of Notch signaling in neural stem cells. Rnd3 deficiency, both in vivo and in vitro, resulted in increased levels of Notch intracellular domain protein. This led to enhanced Notch signaling and promotion of aberrant neural stem cell growth, thereby resulting in a larger subventricular zone and a markedly larger brain. Inhibition of Notch activity abrogated this aberrant neural stem cell growth.

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Neogenin-YAP signaling in neocortical astrocytic differentiation

Cited by 12 publications

References 52 publications

Astrocytic neogenin/netrin-1 pathway promotes blood vessel homeostasis and function in mouse cortex

Astrocytic neogenin/netrin-1 pathway promotes blood vessel homeostasis and function in mouse cortex

A connexin43/YAP axis regulates astroglial-mesenchymal transition in hemoglobin induced astrocyte activation

Genetic deletion of Rnd3 in neural stem cells promotes proliferation via upregulation of Notch signaling

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