The glia-derived extracellular matrix glycoprotein tenascin-C promotes embryonic and postnatal retina axon outgrowth via the alternatively spliced fibronectin type III domain TNfnD
Abstract
Tenascin-C (Tnc) is an astrocytic multifunctional extracellular matrix (ECM) glycoprotein that potentially promotes or inhibits neurite outgrowth. To investigate its possible functions for retinal development, explants from embryonic day 18 (E18) rat retinas were cultivated on culture substrates composed of poly-d-lysine (PDL), or PDL additionally coated with Tnc or laminin (LN)-1, which significantly increased fiber length. When combined with LN, Tnc induced axon fasciculation that reduced the apparent number of outgrowing fibers. In order to circumscribe the stimulatory region, Tnc-derived fibronectin type III (TNfn) domains fused to the human Ig-Fc-fragment TNfnD6-Fc, TNfnBD-Fc, TNFnA 1 A 2-Fc and TNfnA 1 D-Fc were studied. The fusion proteins TNfnBD-Fc and to a lesser degree TNfnA1D-Fc were stimulatory when compared with the Ig-Fc-fragment protein without insert. In contrast, the combination TNfnA 1 A 2-Fc reduced fiber outgrowth beneath the values obtained for the Ig-Fc domain, indicating potential inhibitory properties. The monoclonal J1/tn2 antibody (clone 578) that is specific for domain TNfnD blocked the stimulatory properties of the TNfn-Fc fusions. When postnatal day 7 retinal ganglion cells were used rather that explants, Tnc and Tnc-derived proteins proved permissive for neurite outgrowth. The present study highlights a strong retinal axon growth-promoting activity of the Tnc domain TNfnD, which is modulated by neighboring domains.
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These findings are not easily reconciled with sharp reductions of WFA-positive PNNs, because glial cells represent a main source of CSPGs and other PNN components.
“These findings are not easily reconciled with sharp reductions of WFA-positive PNNs, because glial cells represent a main source of CSPGs and other PNN components.35, 37, 99”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [99]
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Self-citation
- Authors
- Siddiqui, S., Horvat-Bröcker, A., & Faissner, A.
- Affiliations
- Ruhr University Bochum (DE)
- ORCID
- Siddiqui, Sonia
- Venue
- Neuron Glia Biology
- Publisher
- Cambridge University Press (CUP)
- Published
- 2008-11
- Volume
- 4
- Issue
- 4
- Pages
- 271-283
- ISSN
- 1740-925X (ISSN-L)
- 1741-0533
- OpenAlex
- W2122704471
- Cited by
- 30
- References
- 63
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 3 · 2012: 3
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuron Glia Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- tenascin-C, fibronectin type III domain, extracellular matrix glycoprotein, neurite outgrowth, retinal development, laminin-1, axon fasciculation, retinal ganglion cells, alternative splicing, rat retina
- MeSH terms
- Age Factors, Animals, Animals, Newborn, Antibodies, Monoclonal, Axons, Cells, Cultured, Dose-Response Relationship, Drug, Embryo, Mammalian, Female, Fibronectins, Humans, Immunoglobulin Fc Fragments, Laminin, Neural Inhibition, Pregnancy, Recombinant Fusion Proteins, Retina, Retinal Ganglion Cells, Rats, Sprague-Dawley, Alternative Splicing, Protein Structure, Tertiary, Gene Expression Regulation, Developmental, Tenascin, Rats, In Vitro Techniques
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