ArticlePLoS genetics2016
A Mouse Model for Conditional Secretion of Specific Single-Chain Antibodies Provides Genetic Evidence for Regulation of Cortical Plasticity by a Non-cell Autonomous Homeoprotein Transcription Factor.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Choroid plexus modulates subventricular zone adult neurogenesis and olfaction through secretion of small extracellular vesicles.Fluids and barriers of the CNS · 2026Article
- Neurotrophin-3 produced by motor neurons non-cell autonomously regulate the development of pre-motor interneurons in the developing spinal cord.bioRxiv : the preprint server for biology · 2026Article
- Choroid Plexus Modulates Subventricular Zone Adult Neurogenesis and Olfaction Through Secretion of Small Extracellular Vesicles.Research square · 2025Article
- The Pathophysiological Underpinnings of Gamma-Band Alterations in Psychiatric Disorders.Life (Basel, Switzerland) · 2024Review
- Therapeutic value of homeoprotein signaling pathways.Frontiers in neuroscience · 2024Review
- Review
- Disease-causing mutations in genes encoding transcription factors critical for photoreceptor development.Frontiers in molecular neuroscience · 2023Review
- Deconstructing the functional neuroanatomy of the choroid plexus: an ontogenetic perspective for studying neurodevelopmental and neuropsychiatric disorders.Molecular psychiatry · 2022Review
- A Computational Approach to Explaining Bioelectrically Induced Persistent, Stochastic Changes of Axial Polarity in Planarian Regeneration.Bioelectricity · 2022Article
- Non-Cell-Autonomous Factors Implicated in Parvalbumin Interneuron Maturation and Critical Periods.Frontiers in neural circuits · 2022Review
- Shuttling Homeoproteins and Their Biological Significance.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Unconventional Secretion, Gate to Homeoprotein Intercellular Transfer.Frontiers in cell and developmental biology · 2022Review
- Non-cell-autonomous OTX2 transcription factor regulates anxiety-related behavior in the mouse.Molecular psychiatry · 2021Article
- An Extracellular Perspective on CNS Maturation: Perineuronal Nets and the Control of Plasticity.International journal of molecular sciences · 2021Review
- Homeoprotein transduction in neurodevelopment and physiopathology.Science advances · 2020Review
- Choroid Plexus: The Orchestrator of Long-Range Signalling Within the CNS.International journal of molecular sciences · 2020Review
- An evolutionarily-conserved Wnt3/β-catenin/Sp5 feedback loop restricts head organizer activity in Hydra.Nature communications · 2019Article
- Engrailed homeoprotein blocks degeneration in adult dopaminergic neurons through LINE-1 repression.The EMBO journal · 2018Article
- Developmental pathway genes and neural plasticity underlying emotional learning and stress-related disorders.Learning & memory (Cold Spring Harbor, N.Y.) · 2017Review
- Transplantation of GABAergic interneurons for cell-based therapy.Progress in brain research · 2017Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
During postnatal life the cerebral cortex passes through critical periods of plasticity allowing its physiological adaptation to the environment. In the visual cortex, critical period onset and closure are influenced by the non-cell autonomous activity of the Otx2 homeoprotein transcription factor, which regulates the maturation of parvalbumin-expressing inhibitory interneurons (PV cells). In adult mice, the maintenance of a non-plastic adult state requires continuous Otx2 import by PV cells. An important source of extra-cortical Otx2 is the choroid plexus, which secretes Otx2 into the cerebrospinal fluid. Otx2 secretion and internalization requires two small peptidic domains that are part of the DNA-binding domain. Thus, mutating these "transfer" sequences also modifies cell autonomous transcription, precluding this approach to obtain a cell autonomous-only mouse. Here, we develop a mouse model with inducible secretion of an anti-Otx2 single-chain antibody to trap Otx2 in the extracellular milieu. Postnatal secretion of this single-chain antibody by PV cells delays PV maturation and reduces plasticity gene expression. Induced adult expression of this single-chain antibody in cerebrospinal fluid decreases Otx2 internalization by PV cells, strongly induces plasticity gene expression and reopens physiological plasticity. We provide the first mammalian genetic evidence for a signaling mechanism involving intercellular transfer of a homeoprotein transcription factor. Our single-chain antibody mouse model is a valid strategy for extracellular neutralization that could be applied to other homeoproteins and signaling molecules within and beyond the nervous system.
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Registered trials
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.