Title

Molecularly defined cortical astroglia subpopulation modulates neurons via secretion of Norrin

Authors

Sean J. Miller, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Thomas Philips, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Namho Kim, The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Raha Dastgheyb, Department of Neurology, Richard T. Johnson Division of Neuroimmunology and Neurological Infections, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Zhuoxun Chen, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yi-Chun Hsieh, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Gavin Daigle, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Malika Datta, Department of Biological Sciences, Columbia University, New York, NY, USA.
Jeannie Chew, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Svetlana Vidensky, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jacqueline T. Pham, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ethan G. Hughes, Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Michael B. Robinson, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA.
Rita Sattler, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Raju Tomer, Department of Biological Sciences, Columbia University, New York, NY, USA.
Jung Soo Suk, The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Dwight E. Bergles, Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Norman Haughey, Department of Neurology, Richard T. Johnson Division of Neuroimmunology and Neurological Infections, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mikhail Pletnikov, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Justin Hanes, The Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jeffrey D. Rothstein, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. jrothstein@jhmi.edu.

Document Type

Article

Abstract

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.

Medical Subject Headings

Animals; Astrocytes (metabolism); Cells, Cultured; Cerebral Cortex (metabolism); Dendritic Spines (physiology); Eye Proteins (metabolism); Gray Matter (metabolism); Humans; Male; Mice, Inbred C57BL; Mice, Transgenic; Motor Cortex (metabolism); Nerve Tissue Proteins (metabolism); Neurons (metabolism); Receptors, G-Protein-Coupled (metabolism); Transcriptome

Publication Date

5-1-2019

Publication Title

Nature neuroscience

E-ISSN

1546-1726

Volume

22

Issue

5

First Page

741

Last Page

752

PubMed ID

30936556

Digital Object Identifier (DOI)

10.1038/s41593-019-0366-7

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