Molecularly defined cortical astroglia subpopulation modulates neurons via secretion of Norrin

Sean J. Miller, Thomas Philips, Namho Kim, Raha Dastgheyb, Zhuoxun Chen, Yi Chun Hsieh, J. Gavin Daigle, Malika Datta, Jeannie Chew, Svetlana Vidensky, Jacqueline T. Pham, Ethan G. Hughes, Michael B. Robinson, Rita Sattler, Raju Tomer, Jung Soo Suk, Dwight E Bergles, Norman Haughey, Mikhail Pletnikov, Justin S HanesJeffrey D Rothstein

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalNature neuroscience
DOIs
StatePublished - Jan 1 2019

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Astrocytes
Neurons
Dendrites
Spine
Dendritic Spines
G-Protein-Coupled Receptors
Leucine
Transgenic Mice
Rodentia
Ligands
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Molecularly defined cortical astroglia subpopulation modulates neurons via secretion of Norrin. / Miller, Sean J.; Philips, Thomas; Kim, Namho; Dastgheyb, Raha; Chen, Zhuoxun; Hsieh, Yi Chun; Daigle, J. Gavin; Datta, Malika; Chew, Jeannie; Vidensky, Svetlana; Pham, Jacqueline T.; Hughes, Ethan G.; Robinson, Michael B.; Sattler, Rita; Tomer, Raju; Suk, Jung Soo; Bergles, Dwight E; Haughey, Norman; Pletnikov, Mikhail; Hanes, Justin S; Rothstein, Jeffrey D.

In: Nature neuroscience, 01.01.2019.

Research output: Contribution to journalArticle

Miller, Sean J. ; Philips, Thomas ; Kim, Namho ; Dastgheyb, Raha ; Chen, Zhuoxun ; Hsieh, Yi Chun ; Daigle, J. Gavin ; Datta, Malika ; Chew, Jeannie ; Vidensky, Svetlana ; Pham, Jacqueline T. ; Hughes, Ethan G. ; Robinson, Michael B. ; Sattler, Rita ; Tomer, Raju ; Suk, Jung Soo ; Bergles, Dwight E ; Haughey, Norman ; Pletnikov, Mikhail ; Hanes, Justin S ; Rothstein, Jeffrey D. / Molecularly defined cortical astroglia subpopulation modulates neurons via secretion of Norrin. In: Nature neuroscience. 2019.
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