Activity-dependent modulation of synapse-regulating genes in astrocytes
Abstract
Astrocytes regulate the formation and function of neuronal synapses via multiple signals, however, what controls regional and temporal expression of these signals during development is unknown. We determined the expression profile of astrocyte synapse-regulating genes in the developing mouse visual cortex, identifying astrocyte signals that show differential temporal and layer-enriched expression. These patterns are not intrinsic to astrocytes, but regulated by visually-evoked neuronal activity, as they are absent in mice lacking glutamate release from thalamocortical terminals. Consequently, synapses remain immature. Expression of synapse-regulating genes and synaptic development are also altered when astrocyte signaling is blunted by diminishing calcium release from astrocyte stores. Single nucleus RNA sequencing identified groups of astrocytic genes regulated by neuronal and astrocyte activity, and a cassette of genes that show layer-specific enrichment. Thus, the development of cortical circuits requires coordinated signaling between astrocytes and neurons, highlighting astrocytes as a target to manipulate in neurodevelopmental disorders.
Data availability
DATA AVAILABILITYAll data supporting the results of this study can be found in the following locations:Processed RNA sequencing data presented in Figure 1 is available in Figure 1- Source Data 1.Data presented in graphs in Figures 2-5 is available in Figure 2-5 Source Data files.Processed single nucleus RNA sequencing data presented in Figure 6 is available in Figure 6-Source Data 1.The RNA sequencing data has been deposited at GEO. Ribotag data is available at GSE161398 and glial snRNAseq at GSE163775.Processed RNA sequencing data is available in a searchable format at the following web locations:Ribotag astrocyte developmental dataset:igc1.salk.edu:3838/astrocyte_transcriptomeSingle nucleus glial cell sequencing:mouse-astro-dev.cells.ucsc.edu
-
Astrocyte developmental transcriptome from mouse visual cortexNCBI Gene Expression Omnibus, GSE161398.
-
Activity-dependent modulation of synapse-regulating genes in astrocytesNCBI Gene Expression Omnibus, GSE163775.
-
Astrocyte-enriched pan-brain aging transcriptomeNCBI Gene Expression Omnibus, GSE99791.
Article and author information
Author details
Funding
National Institutes of Health (NS105742)
- Nicola J Allen
National Institutes of Health (NS089791)
- Nicola J Allen
Pew Charitable Trusts
- Nicola J Allen
Chan Zuckerberg Initiative (2018-191894)
- Nicola J Allen
Howard Hughes Medical Institute
- Joseph R Ecker
National Institutes of Health (NIH NCI CCSG P30 014195)
- Maxim N Shokhirev
Hearst Foundations
- Nicola J Allen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Beth Stevens, Boston Children's Hospital, United States
Ethics
Animal experimentation: This study was performed in accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal work was approved by the Salk Institute Institutional Animal Care and Use Committee (IACUC) protocol 12-00023.
Version history
- Preprint posted: December 30, 2020 (view preprint)
- Received: May 19, 2021
- Accepted: September 7, 2021
- Accepted Manuscript published: September 8, 2021 (version 1)
- Version of Record published: October 7, 2021 (version 2)
Copyright
© 2021, Farhy-Tselnicker et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 7,344
- views
-
- 967
- downloads
-
- 55
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Developmental Biology
Large-scale cell flow characterizes gastrulation in animal development. In amniote gastrulation, particularly in avian gastrula, a bilateral vortex-like counter-rotating cell flow, called ‘polonaise movements’, appears along the midline. Here, through experimental manipulations, we addressed relationships between the polonaise movements and morphogenesis of the primitive streak, the earliest midline structure in amniotes. Suppression of the Wnt/planar cell polarity (PCP) signaling pathway maintains the polonaise movements along a deformed primitive streak. Mitotic arrest leads to diminished extension and development of the primitive streak and maintains the early phase of the polonaise movements. Ectopically induced Vg1, an axis-inducing morphogen, generates the polonaise movements, aligned to the induced midline, but disturbs the stereotypical cell flow pattern at the authentic midline. Despite the altered cell flow, induction and extension of the primitive streak are preserved along both authentic and induced midlines. Finally, we show that ectopic axis-inducing morphogen, Vg1, is capable of initiating the polonaise movements without concomitant PS extension under mitotic arrest conditions. These results are consistent with a model wherein primitive streak morphogenesis is required for the maintenance of the polonaise movements, but the polonaise movements are not necessarily responsible for primitive streak morphogenesis. Our data describe a previously undefined relationship between the large-scale cell flow and midline morphogenesis in gastrulation.
-
- Developmental Biology
- Physics of Living Systems
Geometric criteria can be used to assess whether cell intercalation is active or passive during the convergent extension of tissue.