Molecularly defined cortical astroglia subpopulation modulates neurons via secretion of Norrin

被引：58

作者：

Miller, Sean J. ^{[1
,2
,3
]}

Philips, Thomas ^{[1
,2
]}

Kim, Namho ^{[4
,5
]}

Dastgheyb, Raha ^{[6
]}

Chen, Zhuoxun ^{[1
,2
]}

Hsieh, Yi-Chun ^{[1
,2
]}

Daigle, J. Gavin ^{[1
,2
]}

Datta, Malika ^{[7
]}

Chew, Jeannie ^{[1
,2
]}

Vidensky, Svetlana ^{[1
,2
]}

Pham, Jacqueline T. ^{[1
,2
,3
]}

Hughes, Ethan G. ^{[8
]}

Robinson, Michael B. ^{[9
,10
]}

Sattler, Rita ^{[1
,2
]}

Tomer, Raju ^{[7
]}

Suk, Jung Soo ^{[4
,11
,12
,13
,14
,15
]}

Bergles, Dwight E. ^{[8
]}

Haughey, Norman ^{[6
,16
]}

Pletnikov, Mikhail ^{[16
]}

Hanes, Justin ^{[4
,5
,11
,12
,13
,14
,15
]}

Rothstein, Jeffrey D. ^{[1
,2
,3
,8
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Brain Sci Inst, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Cellular & Mol Med, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Ctr Nanomed, Baltimore, MD USA

[5] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD USA

[6] Johns Hopkins Univ, Sch Med, Dept Neurol, Richard T Johnson Div Neuroimmunol & Neurol Infec, Baltimore, MD 21205 USA

[7] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA

[8] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA

[9] Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[10] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA

[11] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA

[12] Johns Hopkins Univ, Dept Environm & Hlth Sci, Baltimore, MD USA

[13] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA

[14] Johns Hopkins Univ, Dept Neurosurg, Baltimore, MD USA

[15] Johns Hopkins Univ, Dept Pharmacol & Mol Sci, Baltimore, MD USA

[16] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA

来源：

NATURE NEUROSCIENCE | 2019年 / 22卷 / 05期

基金：

美国国家科学基金会;

关键词：

SPINE LOSS; ASTROCYTES; CELLS; EXPRESSION; SUBTYPE; DISEASE; MODEL; GLIA; HETEROGENEITY; TRANSCRIPTOME;

D O I：

10.1038/s41593-019-0366-7

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Despite expanding knowledge regarding the role of astroglia in regulating neuronal function, little is known about regional or functional subgroups of brain astroglia and how they may interact with neurons. We use an astroglia-specific promoter fragment in transgenic mice to identify an anatomically defined subset of adult gray matter astroglia. Using transcriptomic and histological analyses, we generate a combinatorial profile for the in vivo identification and characterization of this astroglia subpopulation. These astroglia are enriched in mouse cortical layer V; express distinct molecular markers, including Norrin and leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6), with corresponding layer-specific neuronal ligands; are found in the human cortex; and modulate neuronal activity. Astrocytic Norrin appears to regulate dendrites and spines; its loss, as occurring in Norrie disease, contributes to cortical dendritic spine loss. These studies provide evidence that human and rodent astroglia subtypes are regionally and functionally distinct, can regulate local neuronal dendrite and synaptic spine development, and contribute to disease.

引用

页码：741 / +

页数：14

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