Evidence map›Paper›PMID 41720089›Full record

ArticleNeuron2026

Astrocyte-microglia crosstalk through Hevin and Toll-like receptor signaling controls developmental thalamocortical synapse refinement.

Juan J Ramirez, Evelyn J Hardin, Kristina Sakers, Jinhu Kim, Crystal Colón Ortiz, Justin T Savage, Richa Hanamsagar, Carina L Block, Sandeep K Singh, Staci D Bilbo and 1 more

Abstract read
In one paragraph

Article in Neuron, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Juan J RamirezDepartment of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Evelyn J HardinDepartment of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Kristina SakersDepartment of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Howard Hughes Medical Institute, Duke University, Durham, NC 27710, USA.
Jinhu KimDepartment of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Crystal Colón OrtizDepartment of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Justin T SavageDepartment of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
Richa HanamsagarDepartment of Psychology and Neuroscience, Duke University, Durham, NC 27710, USA.
Carina L BlockDepartment of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Sandeep K SinghDepartment of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Staci D BilboDepartment of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA; Department of Psychology and Neuroscience, Duke University, Durham, NC 27710, USA.
Cagla ErogluDepartment of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Howard Hughes Medical Institute, Duke University, Durham, NC 27710, USA. Electronic address: cagla.eroglu@duke.edu.

Funding

Novel Genetically Encoded Indicators for Interrogating Neuron-Astrocyte Communication Across TimescalesU19NS123719 · NINDS · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI TIAN, LIN · 2021 to 2025
$10.7M
URM Student supplement - R01 NS126504 SSinghR01NS126504 · NINDS · VIRGINIA COMMONWEALTH UNIVERSITY · PI Sandeep Kumar Singh · 2022 to 2026
$2.3M
Control of Astrocyte Development and Astrocyte-Synapse InteractionsR01NS102237 · NINDS · DUKE UNIVERSITY · PI EROGLU, CAGLA · 2018 to 2022
$1.9M
A novel role for astrocyte-secreted synaptogenic factor Hevin/SPARCL1 in microglia-mediated synaptic pruning in response to visual experienceF31NS125985 · NINDS · DUKE UNIVERSITY · PI RAMIREZ, JUAN JOSE · 2022 to 2023
$79k
NINDS NIH HHS F31 NS125985NINDS NIH HHS R01 NS102237NINDS NIH HHS R01 NS126504NINDS NIH HHS U19 NS123719
6 · The paper itself

Abstract

Synapse formation and elimination are two crucial processes that occur concurrently in the developing brain. Astrocytes and microglia control both processes, yet how these two major glial cell types of the central nervous system (CNS) communicate to balance synapse formation and elimination is unknown. Astrocytes secrete the synaptogenic protein Hevin/SPARCL1, which induces the formation and plasticity of thalamocortical synapses in the mouse visual cortex. Here, we found that, in addition to this synaptogenic function, Hevin directly signals to microglia by interacting with Toll-like receptor 4 (TLR4). This signaling occurs when Hevin is proteolytically cleaved, producing a C-terminal fragment that is no longer synaptogenic. We found that Hevin, through TLR4, induces a distinct microglial state defined by increased TLR2 expression and phago-lysosomal content in vitro and in vivo. Microglial TLR4 signaling is required for the proper elimination of thalamocortical synapses during early postnatal development.

Indexed as

AstrocytesCalcium-Binding ProteinsCerebral CortexMicrogliaSynapsesThalamusToll-Like Receptor 4Visual CortexAnimalsMiceNeurodevelopmentSignal TransductionCalcium-Binding ProteinsTlr4 protein, mouseToll-Like Receptor 4astrocyteHevin/Sparcl1microgliathalamocortical synapseTLR4

Identifiers

PMID41720089
PMCPMC13242099

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.