ArticleCells2021
Synaptic Hyaluronan Synthesis and CD44-Mediated Signaling Coordinate Neural Circuit Development.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Astrocyte targeted SMN1 gene therapy and forskolin application improves astrocyte filopodia actin defects and motor neuron synaptic dysfunction in human SMA disease pathology.bioRxiv : the preprint server for biology · 2026Article
- Sulforaphane protects developing neural networks from VPA-induced synaptic alterations.Molecular psychiatry · 2025Article
- Expression of CD44 and Its Spliced Variants: Innate and Inducible Roles in Nervous Tissue Cells and Their Environment.International journal of molecular sciences · 2025Review
- Hyaluronan: An Architect and Integrator for Cancer and Neural Diseases.International journal of molecular sciences · 2025Review
- Integrated gene expression and alternative splicing analysis in human and mouse models of Rett syndrome.Scientific reports · 2025Article
- Differential Regulation of Hyaluronan Synthesis by Three Isoforms of Hyaluronan Synthases in Mammalian Cells.Biomolecules · 2024Article
- Developmental patterns of extracellular matrix molecules in the embryonic and postnatal mouse hindbrain.Frontiers in neuroanatomy · 2024Article
- Article
- Interactions between astrocytes and extracellular matrix structures contribute to neuroinflammation-associated epilepsy pathology.Frontiers in molecular medicine · 2023Review
- Brain Targeting of Citicoline Sodium via Hyaluronic Acid-Decorated Novel Nano-Transbilosomes for Mitigation of Alzheimer's Disease in a Rat Model: Formulation, Optimization, in vitro and in vivo Assessment.International journal of nanomedicine · 2022Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hyaluronan-based extracellular matrix is expressed throughout nervous system development and is well-known for the formation of perineuronal nets around inhibitory interneurons. Since perineuronal nets form postnatally, the role of hyaluronan in the initial formation of neural circuits remains unclear. Neural circuits emerge from the coordinated electrochemical signaling of excitatory and inhibitory synapses. Hyaluronan localizes to the synaptic cleft of developing excitatory synapses in both human cortical spheroids and the neonatal mouse brain and is diminished in the adult mouse brain. Given this developmental-specific synaptic localization, we sought to determine the mechanisms that regulate hyaluronan synthesis and signaling during synapse formation. We demonstrate that hyaluronan synthase-2, HAS2, is sufficient to increase hyaluronan levels in developing neural circuits of human cortical spheroids. This increased hyaluronan production reduces excitatory synaptogenesis, promotes inhibitory synaptogenesis, and suppresses action potential formation. The hyaluronan receptor, CD44, promotes hyaluronan retention and suppresses excitatory synaptogenesis through regulation of RhoGTPase signaling. Our results reveal mechanisms of hyaluronan synthesis, retention, and signaling in developing neural circuits, shedding light on how disease-associated hyaluronan alterations can contribute to synaptic defects.
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