Developmental expression of FMRP in the astrocyte lineage: Implications for fragile X syndrome.
Abstract
One of the most common causes of mental retardation in humans, Fragile X syndrome, results from the absence of FMRP, the protein product of the FMR1 gene. In the nervous system, expression of FMRP has been thought to be confined mainly to neurons as little research has examined FMRP expression in non-neuronal lineages. We present evidence that, in addition to neuronal expression, FMRP is expressed in developing CNS glial cells in vitro and in vivo. The neurosphere assay was used to establish cultures of stem and progenitor cells from the brains of wildtype and FMRP knockout (B6.129.FMR1/FvBn) mouse pups. When the neurospheres were differentiated in vitro, approximately 50% of the FMRP positive cells also expressed GFAP. Immunocytochemical studies of the embryonic and postnatal mouse brain revealed coexpression of FMRP and GFAP in the developing hippocampus. Prominent coexpression was also observed in ependymal cells surrounding the third ventricle and astrocytes of the glia limitans. No double-labeled cells were evident in the brains of young adult mice. Cells coexpressing FMRP and the oligodendrocyte precursor marker NG2 were also identified in the hippocampus and corpus callosum of the early postnatal brain. Our results suggest that FMRP is expressed in cells of non-neuronal lineage(s) during development. This represents potential involvement of glial cells in the neural development of fragile X syndrome.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the CNS, FMRP is expressed in neurons and during development in glial cells.
“In the CNS, it is expressed in neurons and during development in glial cells.”
From Astrocytes in fragile X syndrome (2024) · cites this paper as Pacey and Doering, 2007
FMRP expression in astrocytes shows highest levels at the time of vital growth, stabilization, and maturation of synapses, declining thereafter.
“Its expression in astrocytes shows highest levels at the time of vital growth, stabilization, and maturation of synapses, declining thereafter (Pacey and Doering, 2007).”
From Astrocytes in fragile X syndrome (2024) · cites this paper as Pacey and Doering, 2007
Astrocytes express FMRP during development, and its absence influences the way astrocytes differentiate in both human and murine models of FXS.
“Astrocytes express FMRP during development (Pacey and Doering, 2007; Gholizadeh et al., 2015), and its absence influences the way astrocytes differentiate in both human and murine models of FXS.”
From Astrocytes in fragile X syndrome (2024) · cites this paper as Pacey and Doering, 2007
Cites
Astrocytic Purinergic Signaling Coordinates Synaptic Networks
Pascual, O., Casper, K. B., Kubera, C., Zhang, J., Revilla-Sanchez, R., Sul, J.-Y., Takano, H., Moss, S. J., McCarthy, K., & Haydon, P. G. (2005) · Science · doi:10.1126/science.1116916 · Cited by 1,280 · see citing works
Control of hippocampal dendritic spine morphology through ephrin-A3/EphA4 signaling
Murai, K. K., Nguyen, L. N., Irie, F., Yamaguchi, Y., & Pasquale, E. B. (2003) · Nature Neuroscience · doi:10.1038/nn994 · Cited by 516 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Astrocytes and disease: a neurodevelopmental perspective
Molofsky, A. V., Krenick, R., Ullian, E., Tsai, H.-H., Deneen, B., Richardson, W. D., Barres, B. A., & Rowitch, D. H. (2012) · Genes & Development · doi:10.1101/gad.188326.112 · Cited by 682 · see citing works
The Indispensable Roles of Microglia and Astrocytes during Brain Development
Reemst, K., Noctor, S. C., Lucassen, P. J., & Hol, E. M. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00566 · Cited by 516 · see citing works
Olmos-Serrano, J. L., Paluszkiewicz, S. M., Martin, B. S., Kaufmann, W. E., Corbin, J. G., & Huntsman, M. M. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1714-10.2010 · Cited by 309 · see citing works
CGG repeat in the FMR1 gene: size matters
Willemsen, R., Levenga, J., & Oostra, B. (2011) · Clinical Genetics · doi:10.1111/j.1399-0004.2011.01723.x · Cited by 184 · see citing works
Higashimori, H., Schin, C. S., Chiang, M. S. R., Morel, L., Shoneye, T. A., Nelson, D. L., & Yang, Y. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.1069-16.2016 · Cited by 105 · see citing works
Fatemi, S. H., & Folsom, T. D. (2011) · Molecular Autism · doi:10.1186/2040-2392-2-6 · Cited by 84 · see citing works
Aberrant differentiation of glutamatergic cells in neocortex of mouse model for fragile X syndrome.
Tervonen, T. A., Louhivuori, V., Sun, X., Hokkanen, M.-E., Kratochwil, C. F., Zebryk, P., Castrén, E., & Castrén, M. L. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.10.010 · Cited by 82 · see citing works
The role of fragile X mental retardation protein in major mental disorders
Fatemi, S. H., & Folsom, T. D. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.11.011 · Cited by 80 · see citing works
Heads‐up: New roles for the fragile X mental retardation protein in neural stem and progenitor cells
Callan, M. A., & Zarnescu, D. C. (2011) · genesis · doi:10.1002/dvg.20745 · Cited by 39 · see citing works
Wallingford, J., Scott, A. L., Rodrigues, K., & Doering, L. C. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00268 · Cited by 38 · see citing works
Self-citationThe neurochemical basis for the treatment of autism spectrum disorders and Fragile X syndrome
Hampson, D. R., Adusei, D. C., & Pacey, L. K. K. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.02.005 · Cited by 34 · see citing works
Self-citationAstrocytes in fragile X syndrome
Talvio, K., & Castrén, M. L. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1322541 · Cited by 8 · see citing works
- Authors
- Pacey, L. K. K., & Doering, L. C.
- Affiliations
- McMaster University (CA)
- Corresponding author
- Doering, Laurie C.
- ORCID
- Pacey, Laura K. K.
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2007-09-06
- Volume
- 55
- Issue
- 15
- Pages
- 1601-1609
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2021949049
- Cited by
- 128
- References
- 2
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 3 · 2023: 3 · 2022: 8 · 2021: 1 · 2020: 8 · 2019: 4 · 2018: 5 · 2017: 6 · 2016: 11 · 2015: 7 · 2014: 11 · 2013: 12 · 2012: 10
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Brown University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- FMRP, fragile X syndrome, astrocytes, glial cells, FMR1 gene, glial fibrillary acidic protein, NG2, oligodendrocyte precursor cells, neurospheres, hippocampus, glia limitans, ependymal cells, neural development
- MeSH terms
- Animals, Astrocytes, Brain, Cell Differentiation, Cell Wall, Fragile X Syndrome, Genetic Markers, Glial Fibrillary Acidic Protein, Neurons, Oligodendroglia, Synapses, Mice, Knockout, Gene Expression Regulation, Developmental, Cell Lineage, Third Ventricle, Mice, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
