Molecularly defined cortical astroglia subpopulation modulates neurons via secretion of Norrin

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 grey matter astroglia. Using transcriptomic and histological analyses, we generate a combinatorial profile for in vivo identification and characterization of this astroglia subpopulation. These astroglia are enriched in cortical layer V, express distinct molecular markers, including norrin and LGR6, with corresponding layer-specific neuronal ligands, are found in human cortex and modulate neuronal activity. Astrocytic norrin appears to regulate dendrites and spines and its loss, as occurs 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.

Cell Atlas of the Human Fovea and Peripheral Retina

“…8h). In addition, however, NDP and LRP5 were also expressed in Müller glia (41) and in astrocytes, a finding compatible with observations of NDP expression in a subset of cortical astrocytes (42) Age Related Macular Degeneration (AMD) is broadly classified into non-exudative ("dry") and exudative or neovascular ("wet") types. In dry AMD mild forms are characterized by drusen accumulation between retinal pigment epithelium and Bruch's membrane, which can progress to late forms with large patches of atrophic outer retina.…”

Role of Human-Induced Pluripotent Stem Cell-Derived Spinal Cord Astrocytes in the Functional Maturation of Motor Neurons in a Multielectrode Array System

“…The following electrophysiological parameters were analyzed: spike frequency, burst rate, and percentage of spiking and bursting electrodes. Functional connectivity graphs based on spike frequency were generated as recently described . The recording of the baseline activity of MEA plates was performed weekly over a 1‐minute period for 4 weeks after plating.…”

Identification of region-specific astrocyte subtypes at single cell resolution

“…In addition, astrocytes in different brain regions also have distinct morphological and functional features, such as degree of synapse association 9,10 , intrinsic membrane properties and Ca 2+ signaling 10 , and ability to promote neuronal maturation 12 . Refined labeling strategies using promoter fragments 13 , or intersectional approaches 14,15 to isolate subpopulations of cells have revealed intra-regional heterogeneity in the cortex [13][14][15] , as well as the brainstem, thalamus, olfactory bulb, cerebellum and spinal cord 14 , which again correlates to morphology 15 , cell intrinsic physiology 15 and function 13,14 .…”