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000277315 0247_ $$2doi$$a10.1126/scisignal.adl6745
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000277315 037__ $$aDZNE-2025-00378
000277315 041__ $$aEnglish
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000277315 1001_ $$00000-0003-3107-016X$$aSona, Chandan$$b0
000277315 245__ $$aGlutamatergic argonaute2 promotes the formation of the neurovascular unit in mice.
000277315 260__ $$aWashington, DC [u.a.]$$bAssoc.$$c2025
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000277315 520__ $$aProper formation of the complex neurovascular unit (NVU) along with the blood-brain barrier is critical for building and sustaining a healthy, functioning central nervous system. The RNA binding protein argonaute2 (Ago2) mediates microRNA (miRNA)-mediated gene silencing, which is critical for many facets of brain development, including NVU development. Here, we found that Ago2 in glutamatergic neurons was critical for NVU formation in the developing cortices of mice. Glutamatergic neuron-specific loss of Ago2 diminished synaptic formation, neuronal-to-endothelial cell contacts, and morphogenesis of the brain vasculature, ultimately compromising the integrity of the blood-brain barrier. Ago2 facilitated miRNA targeting of phosphatase and tensin homolog (Pten) mRNA, which encodes a phosphatase that modulates reelin-dependent phosphatidylinositol 3-kinase (PI3K)-Akt signaling within the glutamatergic subpopulation. Conditionally deleting Pten in Ago2-deficient neurons restored Akt2 phosphorylation as well as postnatal development and survival. Several mutations in AGO2 impair small RNA silencing and are associated with Lessel-Kreienkamp syndrome, a neurodevelopmental disorder. When expressed in a neuronal cell line, these human AGO2 loss-of-function variants failed to suppress PTEN, resulting in attenuated PI3K-Akt signaling, further indicating that dysregulation of Ago2 function may contribute to both impaired development and neurological disorders. Together, these results identify Ago2 as central to the engagement of neurons with blood vessels in the developing brain.
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000277315 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000277315 650_7 $$2NLM Chemicals$$aArgonaute Proteins
000277315 650_7 $$0EC 3.1.3.67$$2NLM Chemicals$$aPTEN Phosphohydrolase
000277315 650_7 $$2NLM Chemicals$$aAgo2 protein, mouse
000277315 650_7 $$0EC 3.4.21.-$$2NLM Chemicals$$aReln protein, mouse
000277315 650_7 $$2NLM Chemicals$$aReelin Protein
000277315 650_7 $$0EC 3.4.21.-$$2NLM Chemicals$$aRELN protein, human
000277315 650_7 $$0EC 3.1.3.67$$2NLM Chemicals$$aPten protein, mouse
000277315 650_7 $$2NLM Chemicals$$aMicroRNAs
000277315 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$aProto-Oncogene Proteins c-akt
000277315 650_7 $$0EC 2.7.1.-$$2NLM Chemicals$$aPhosphatidylinositol 3-Kinases
000277315 650_7 $$2NLM Chemicals$$aAGO2 protein, human
000277315 650_7 $$03KX376GY7L$$2NLM Chemicals$$aGlutamic Acid
000277315 650_2 $$2MeSH$$aAnimals
000277315 650_2 $$2MeSH$$aArgonaute Proteins: metabolism
000277315 650_2 $$2MeSH$$aArgonaute Proteins: genetics
000277315 650_2 $$2MeSH$$aPTEN Phosphohydrolase: metabolism
000277315 650_2 $$2MeSH$$aPTEN Phosphohydrolase: genetics
000277315 650_2 $$2MeSH$$aMice
000277315 650_2 $$2MeSH$$aHumans
000277315 650_2 $$2MeSH$$aNeurons: metabolism
000277315 650_2 $$2MeSH$$aReelin Protein
000277315 650_2 $$2MeSH$$aMicroRNAs: metabolism
000277315 650_2 $$2MeSH$$aMicroRNAs: genetics
000277315 650_2 $$2MeSH$$aSignal Transduction
000277315 650_2 $$2MeSH$$aBlood-Brain Barrier: metabolism
000277315 650_2 $$2MeSH$$aProto-Oncogene Proteins c-akt: metabolism
000277315 650_2 $$2MeSH$$aProto-Oncogene Proteins c-akt: genetics
000277315 650_2 $$2MeSH$$aPhosphatidylinositol 3-Kinases: metabolism
000277315 650_2 $$2MeSH$$aPhosphatidylinositol 3-Kinases: genetics
000277315 650_2 $$2MeSH$$aMice, Knockout
000277315 650_2 $$2MeSH$$aGlutamic Acid: metabolism
000277315 7001_ $$00000-0001-7968-6081$$aYeh, Yu-Te$$b1
000277315 7001_ $$00009-0006-6992-9098$$aLi, Yunxiao$$b2
000277315 7001_ $$aLiu, Xiaoxuan$$b3
000277315 7001_ $$00000-0002-5160-4571$$aGhosh, Adhideb$$b4
000277315 7001_ $$00000-0002-4226-0009$$aHinte, Laura C$$b5
000277315 7001_ $$00000-0003-0963-2461$$aKu, Min-Chi$$b6
000277315 7001_ $$aRathjen, Thomas$$b7
000277315 7001_ $$00000-0001-7584-6527$$aNiendorf, Thoralf$$b8
000277315 7001_ $$00000-0002-5194-8614$$aYu, Guoxing$$b9
000277315 7001_ $$00000-0001-8595-9314$$aJia, Shiqi$$b10
000277315 7001_ $$aKononenko, Natalia L$$b11
000277315 7001_ $$0P:(DE-2719)2811732$$aHermann, Andreas$$b12
000277315 7001_ $$00000-0001-5169-3095$$aLuo, Jiankai$$b13
000277315 7001_ $$00000-0001-9300-1771$$aLin, Juntang$$b14
000277315 7001_ $$00000-0001-9920-3075$$avon Meyenn, Ferdinand$$b15
000277315 7001_ $$0P:(DE-HGF)0$$aYan, Xin$$b16
000277315 7001_ $$00000-0002-4904-2426$$aPoy, Matthew N$$b17
000277315 773__ $$0PERI:(DE-600)2417226-1$$a10.1126/scisignal.adl6745$$gVol. 18, no. 875, p. eadl6745$$n875$$peadl6745$$tScience signaling$$v18$$x1945-0877$$y2025
000277315 8564_ $$uhttps://pub.dzne.de/record/277315/files/DZNE-2025-00378_Restricted.pdf
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