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Written by | Su Yixun Responsible editor| Wang Sizhen
In the central nervous system, oligodendrocytes form myelin-enveloping neuronal axons, which play an important supporting role in rapid nerve impulse conduction[1].
Therefore, the widespread distribution of oligodendrocytes in the central nervous system is critical
.
However, oligodendrocytes (OPCs) are formed in only a few limited regions during development (e.
g.
, MGE and LGE in embryonic stage in the brain, SVZ after birth).
[2] , and requires long-distance migration to finally achieve the distribution of the whole central nervous system [3].
Professor Niu's article published in Science in 2016 revealed that OPC uses cerebrovascular vessels as scaffolds for migration [4].
However, how OPCs detach from the vessels after migration to their destination, and whether the detachment of OPCs from the vessels is a prerequisite for their differentiation, remains unknown.
On November 15, 2022, Niu Jianqin's team from Army Medical University, Yi Chenju's team from the Seventh Affiliated Hospital of Sun Yat-sen University, and the University of California, San Francisco Professor Stephen Fancy co-published in Neuron Research paper "Astrocyte endfoot formation controls the termination of oligodendrocyte precursor cell perivascular migration during neocortical development.
"
The study revealed the coupling mechanism by which the footprocess of developing astrocytes prompts OPCs to leave blood vessels and differentiate at the migration endpoint.
(Extended reading: The relevant research progress of Niu Jianqin's research group, see the "Logical Neuroscience" report for details (click to read): Brain—Yi Chenju/Niu Jianqin's team discovered the activation of Wnt/ The β-catenin pathway alleviates blood-brain barrier dysfunction in Alzheimer's disease; The Mol Psychiatry—Niu Jianqin/Xiao Lan team found that oligodendroid glial precursor cells DISC-Δ3 variable shear inhibited excitatory synaptic growth, leading to schizophrenia; The Mol Psychiatry—Niu Jianqin/Xiao Lan team found that oligodendroid precursor cells DISC-Δ3 variable shear inhibits excitatory synaptic growth, leading to schizophrenia).
In order to study the mechanism of OPC detachment from blood vessels, the authors first focused on the morphological changes of glial cells in the central nervous system in the development time and space, and found that the formation of astrocyte foot processes showed a significant negative correlation with OPC-blood vessel interaction in time and space
。 Morphologically, the astrocytes foot process is between OPC and blood vessels, separating
the two.
The authors label astrocyte (GFP) and OPC (tdTomato) by breeding Aldh1l1-eGFP:NG2-CreERT:LSL-tdTomato mice, respectively ), and intravenous injection of Lectin-Dylight 649 labeled blood vessels, enabling in vivo imaging
of astrocytes, oligodendrocytes lineage cells, and blood vessels in mouse brains.
It was found that foot process formation in astrocytes was strongly associated with OPC detachment from blood vessels (Figure 1).
To further validate the necessity of astrocytes foot formation to promote OPC detachment from blood vessels, the authors established two models (two-photon laser elimination of astrocytes (Figure 1)).
, as well as conditioned expression of DTA to eliminate astrocytes), and an increase in OPC-vascular interaction was observed in
both models.
Description: Astrocytes have an important
role in the detachment of OPCs from blood vessels.
Figure 1 Astrocytes foot process growth promotes OPC detachment from blood vessels (Source: Y.
Su, et al.
, Neuron, 2022
From the perspective of cell development, it is speculated that when OPC migrates with blood vessels as scaffolds, there should be some mechanism to inhibit its premature differentiation, which is conducive to the spread in the whole central nervous system, but there has been a lack of relevant experimental evidence
.
In this study, the authors found that the interaction between mature oligodendrocytes and blood vessels was significantly reduced compared with OPC, suggesting that blood vessels may have inhibited OPC differentiation
.
Further in vitro experiments confirmed that cerebrovascular endothelial cells can inhibit OPC differentiation through contact and secretion (Figure 2).
While in mouse models that eliminated astrocytes, due to OPC Increased interaction with blood vessels, decreased OPC differentiation and myelination
.
Therefore, the detachment of OPCs from blood vessels is necessary for their normal differentiation
.
Figure 2 Inhibition of OPC differentiation by cerebral vascular endothelial cells (Source: Y.
Su, et al.
, Neuron, 2022)
In order to explore the mechanism by which astrocytes promote the detachment of OPCs from blood vessels, the authors analyzed the potential interaction proteins between astrocytes and OPC surfaces through proteomics The chemical repulsion of Semaphorin-plexin may be involved in the regulation of OPC migration [5], so it is speculated: astrocytes The interaction between Semaphorin and OPC Plexin may mediate the process by which astrocytes regulate OPC vascular detachment.
Although Sema3a/6a did not have a direct effect on OPC differentiation in in vitro experiments, the expression of Sema3a/6a in in vivo knockdown astrocyte could be increased OPC-vascular interaction keeps more OPCs in contact with the vessels, thereby inhibiting OPC differentiation
.
Conversely, overexpression of Sema3a in astrocytes can promote OPC detachment from blood vessels, thereby increasing OPC differentiation
.
These evidence suggests that during development, astrocytes can promote the detachment of OPCs from blood vessels through Sema3a/6a, allowing subsequent differentiation
.
Figure 3: Astrocytes promote the detachment of OPCs from blood vessels via Sema3a/6a for subsequent differentiation (Source: Y.
Su, et al.
, Neuron, 2022)
Figure 4 working model (Source: Y.
Su, et al.
, Neuron, 2022)
Conclusion and discussion, inspiration and prospectsIn summary, this study reveals the coupling mechanism between astrocytes foot process formation and oligodendrocytes precursor cell migration and differentiation
。 In the process of migration of oligodendroid glial precursor cells (OPCs) using blood vessels as scaffolds, vascular endothelial cells inhibit premature differentiation of OPCs.
At the end of OPC migration, the foot process formed by astrocytes on the surface of blood vessels promotes OPC to detach from blood vessels, allowing OPCs to differentiate into mature oligodendrocytes (Figure 4)
。 However, the mechanism by which OPCs and astrocytes express a variety of Semaphorin molecules and Plexin receptors in development is not clear
.
Whether these Semaphorin-Plexin interactions are responsible for the mutual exclusion of glial cells in the central nervous system to form a uniform distribution needs further investigation
.
Subsequently, the modes and mechanisms
of interaction between different types of cells during nervous system development and regeneration can be further explored.
Original link: https://doi.
org/10.
1016/j.
neuron.
2022.
10.
032
Su Yixun, assistant researcher of Army Medical University and the Seventh Affiliated Hospital of Sun Yat-sen University, is the co-first author
of this paper.
Professor Stephen Fancy of the University of California, San Francisco (UCSF), Associate Researcher Yi Chenju of the Seventh Affiliated Hospital of Sun Yat-sen University, and Professor Niu Jianqin of the Army Medical University ( Lead Contact) is the co-corresponding author
of this article.
About the author (swipe up and down to read).
Army Medical University.
He was selected as a young Yangtze River scholar of the Ministry of Education of the People's Republic of China, and a Chongqing talent.
He has carried out postdoctoral research
at the Ecole de France and the University of California, San Francisco.
In recent years, he has focused on the development process, regulatory mechanism, and new role
of participation in the development of disease course of oligodendroid glial precursor cells of the central nervous system.
Related research is available in Science, Nature Neuroscience, Neuron, Advanced Science Published in Molecularpsychiatry, Brain, Glia and other magazines.
Yi Chenju: Associate researcher, doctoral supervisor
.
He has won the "Jieqing" of Guangdong Province, the "Excellent Qing" of Shenzhen, the overseas high-level talents of Shenzhen, and the outstanding talents of young and middle-aged talents of the "Hundred Talents Program" of Sun Yat-sen University
.
In 2011, he received his Ph.
D.
degree in neurology from Tongji Hospital, Huazhong University of Science and Technology, and his doctorate degree (MD) in Medicine from the University of Tübingen, Germany.
After that, he worked as a postdoctoral fellow at the Ecole de France and the French Academy of Sciences in Paris, France, and as a Senior Research Fellow
at the Life Research Center of the National University of Singapore.
At the end of 2018, he established a research group in the Seventh Affiliated Hospital of Sun Yat-sen University, mainly engaged in the research
of the mechanism of glial cells in central nervous system diseases.
In Neuron, EMBOJ, Brain, AnnNeurol, AdvSci , Glia and other magazines published more than 50 articles
.
Stephen Fancy is a professor at the University of California, San Francisco, and an internationally recognized research scientist
on oligodendrocytes and white matter.
It has made important contributions to the way oligodendrocytes develop and regenerate, as well as the regulatory mechanism of the Wnt signaling pathway.
Received the NancyDavis Foundation Race to Erase MS Young Investigator Award and the Harry Weaver Scholar of the National Multiple Sclerosis Society
。 In Science, NatNeurosci, GenesDev, Neuron, Brain , PNAS and other published papers
.
Welcome to scan the code to join Logical Neuroscience Literature Study 2
Group Note Format: Name--Field of Research-Degree/Title/Title/PositionSelected Previous Articles【1】Cell Reports | Zhang Jiyan's team revealed the presence and characteristics of hematopoietic stem cells in the meninges of adult mice
[2] The Neurosci Bull-Wang Shouyan/Qiu Zilong team reported abnormal prefrontal nerve oscillations associated with social disorders in MECP2 doubling syndrome
[3] Transl PsychiatryLaibin/Zheng Ping's research group revealed that CREB and GR mediate chronic morphine-induced decrease in miR-105 in the medial prefrontal cortex
[4] iScience—Columbia University Peng Yueqing's team revealed that sensory input regulates abnormal EEG in mice with absence epilepsy through the thalamic cortex pathway
[5] The INT J CANCER-LIANG XIA/LIANG PENG TEAM REVEALED THAT GLIOMA CELL-NEURON SYNAPTIC CONNECTIONS ARE IMPORTANT FACTORS AFFECTING THE SPATIAL PATHOGENESIS OF CELL TUMORS
[6] Neurology—Liyuan Han's team systematically assessed the global and regional and national burden of stroke among young adults
【7】 The GLIA-Baek Hyun-Sook/Frank Kirchhoff team found that a group of OPCs did not express Olig2, and that acute brain injury and learning activities promoted the formation of this group of cells
【8】 Protein Sci—Wang Shuyu's team reported that Bayesian binding to graph neural networks predicted the effect of mutations on protein stability
【9】 Dev Cell—Tian Ye's team found that the GPCR signaling pathway coordinates the body's mitochondrial stress response in a pair of sensory neurons
【10】 J Neurol—melanin-sensitive magnetic resonance imaging studies reveal blue spot degeneration and cerebellar volume changes in patients with essential tremor
Recommended high-quality scientific research training courses [1] The 10th NIR Training Camp (online: 2022.11.
30~12.
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24) Welcome to join "Logical Neuroscience" [1] " Logical Neuroscience " Recruitment Editor/Operation Position ( Online Office [2] Talent Recruitment - "Logical Neuroscience" Recruitment Article Interpretation/Writing Position ( Online Part-time, Online Office) References (swipe up and down to read).
1.
Funfschilling, U.
,et al.
, Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity.
Nature, 2012.
485(7399): p.
517-21.
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Kessaris, N.
,et al.
, Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage.
Nat Neurosci, 2006.
9(2): p.
173-9.
3.
Tsai, H.
H.
,et al.
, The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration.
Cell,2002.
110(3): p.
373-83.
4.
Tsai, H.
H.
,et al.
, Oligodendrocyte precursors migrate along vasculature in the developing nervous system.
Science, 2016.
351(6271): p.
379-84.
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Bernard, F.
,et al.
, Role of transmembrane semaphorin Sema6A in oligodendrocyte differentiation and myelination.
Glia,2012.
60(10): p.
1590-604.
End of article
