Distribution and synthesis of extracellular matrix proteoglycans, hyaluronan, link proteins and tenascin‐R in the rat spinal cord
Abstract
Perineuronal nets (PNNs) are dense extracellular matrix (ECM) structures that form around many neuronal cell bodies and dendrites late in development. They contain several chondroitin sulphate proteoglycans (CSPGs), hyaluronan, link proteins and tenascin‐R. Their time of appearance correlates with the ending of the critical period for plasticity, and they have been implicated in this process. The distribution of PNNs in the spinal cord was examined using Wisteria floribunda agglutinin lectin and staining for chondroitin sulphate stubs after chondroitinase digestion. Double labelling with the neuronal marker, NeuN, showed that PNNs were present surrounding ∼ 30% of motoneurons in the ventral horn, 50% of large interneurons in the intermediate grey and 20% of neurons in the dorsal horn. These PNNs formed in the second week of postnatal development. Immunohistochemical staining demonstrated that the PNNs contain a mixture of CSPGs, hyaluronan, link proteins and tenascin‐R. Of the CSPGs, aggrecan was present in all PNNs while neurocan, versican and phosphacan/RPTPβ were present in some but not all PNNs. In situ hybridization showed that aggrecan and cartilage link protein (CRTL 1) and brain link protein‐2 (BRAL 2) are produced by neurons. PNN‐bearing neurons express hyaluronan synthase, and this enzyme and phosphacan/RPTPβ may attach PNNs to the cell surface. During postnatal development the expression of link protein and aggrecan mRNA is up‐regulated at the time of PNN formation, and these molecules may therefore trigger their formation.
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Crtl-1 is found only in PNNs but not in loose ECM.
“this protein is found only in PNNs but not in loose ECM (Galtrey et al., 2008)”
From Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity (2016) · cites this paper as Galtrey et al., 2008
PNNs containing aggrecan and brevican do not always overlap in mouse somatosensory cortex.
“PNNs containing aggrecan and brevican do not always overlap in mouse somatosensory cortex (Galtrey et al., 2008; Ueno et al., 2017b).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Galtrey et al., 2008
Aggrecan is present on almost all PNN-positive neurons, while other lecticans are found on subpopulations of PNN neurons.
“Aggrecan is present on almost all PNN-positive neurons, while other lecticans are found on subpopulations of PNN neurons, as shown by co-labeling of WFA with antibodies against different CSPG core proteins (Galtrey et al., 2008).”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Galtrey et al., 2008
Hapln1/Crtl1 and Hapln4/Bral2 are expressed exclusively in neurons bearing a perineuronal net.
“These Haplns are expressed exclusively in neurons bearing a PNN (Bekku et al., 2003;Carulli et al., 2006;Galtrey et al., 2008;Rauch et al., 2004) and are essential for the proper assembly of the PNN structure.”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Galtrey et al., 2008
Neurons in the cerebellar nuclei and visual cortex express HAS-2 and HAS-3, while neurons in the spinal cord express HAS-1 and HAS-3.
“Neurons in the cerebellar nuclei and visual cortex express HAS-2 and -3, while neurons in the spinal cord express HAS-1 and -3 (Carulli et al., 2006(Carulli et al., , 2010;;Galtrey et al., 2008).”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Galtrey et al., 2008
In the mature spinal cord, HAS-3 is the only hyaluronan synthase isoform identified.
“However, while HAS-1 and HAS-3 are expressed in developing spinal cord, HAS-3 is the only isoform identified in the mature spinal cord (Galtrey et al., 2008).”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Galtrey et al., 2008
Hapln1/Crtl1 and Hapln4/Bral2 are essential for proper assembly of the perineuronal net structure.
“These Haplns are expressed exclusively in neurons bearing a PNN (Bekku et al., 2003;Carulli et al., 2006;Galtrey et al., 2008;Rauch et al., 2004) and are essential for the proper assembly of the PNN structure.”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Galtrey et al., 2008
The two link proteins found in perineuronal nets are Hapln1/Crtl1 and Hapln4/Bral2.
“Two are the link proteins found in PNNs: Hapln1/Crtl1 and Hapln4/Bral2.”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Galtrey et al., 2008
Within the ventral horn, structural stability-related genes included components of perineuronal nets such as Tnr (Tenascin-R), as well as adhesion molecules such as Sdk1 and intracellular signaling components such as Ptpn5 (STEP).
“Within the ventral horn, this included components of perineuronal nets (which are thought to restrict plasticity and had been previously detected in the ventral spinal cord110,111) such as Tnr (Tenascin-R), as well as adhesion molecules such as Sdk1 and intracellular signaling components such as Ptpn5 (STEP) which de-phosphorylates CAMK2α, NMDA receptors, and ERK kinases33.”
From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [111]
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- Authors
- Galtrey, C. M., Kwok, J. C. F., Carulli, D., Rhodes, K. E., & Fawcett, J. W.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Fawcett, James W.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2008-03
- Volume
- 27
- Issue
- 6
- Pages
- 1373-1390
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2130512993
- Cited by
- 203
- References
- 15
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 9 · 2023: 9 · 2022: 14 · 2021: 8 · 2020: 9 · 2019: 8 · 2018: 21 · 2017: 17 · 2016: 16 · 2015: 8 · 2014: 11 · 2013: 9 · 2012: 12
- FWCI
- 4.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Christopher and Dana Reeve Foundation
- Wellcome Trust (070467)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- perineuronal nets, extracellular matrix proteoglycans, chondroitin sulfate proteoglycans, hyaluronic acid, link protein, tenascin-R, aggrecan, neurocan, versican, phosphacan, RPTPβ/ζ, spinal cord, postnatal development, motor neurons, interneurons, dorsal horn, hyaluronan synthase, neuroplasticity, critical period
- MeSH terms
- Proteoglycan Link Protein, Animals, Animals, Newborn, Dendrites, Extracellular Matrix, Hyaluronic Acid, Neurons, Proteoglycans, Spinal Cord, Extracellular Matrix Proteins, Rats, Sprague-Dawley, Gene Expression Regulation, Developmental, Tenascin, Rats
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