Altered maturation of the primary somatosensory cortex in a mouse model of fragile X syndrome
Abstract
Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and results from the loss of the fragile X mental retardation protein (FMRP). Many fragile X-related cognitive and behavioral features emerge during childhood and are associated with abnormal synaptic and cellular organization of the cerebral cortex. Identifying the roles of FMRP in cortical development will provide a basis for understanding the pathogenesis of the syndrome. However, how the loss of FMRP influences the developmental trajectory of cortical maturation remains unclear. We took advantage of the stereotyped and well-characterized development of the murine primary somatosensory cortex to examine cortical maturation during a time-window that corresponds to late embryonic and early postnatal development in the human. In the Fmr1 knockout mouse, we find a delay in somatosensory map formation, alterations in the morphology profile of dendrites and spines of layer 4 neurons and a decrease in the synaptic levels of proteins involved in glutamate receptor signaling at times corresponding to the highest levels of FMRP expression. In contrast, cortical arealization, synaptic density in layer 4 and early postnatal regulation of mRNAs encoding synaptic proteins are not altered in Fmr1 knockout mice. The specificity of the developmental delay in Fmr1 knockout mice indicates that the loss of FMRP does not result in a general stalling of cerebral cortex maturation. Instead, our results suggest…
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?
Fmr1 mutant mice have a significant delay in the stabilization of dendritic spines and in the maturation of thalamocortical and corticocortical synapses, defects associated with a temporal shift in the critical period for sensory-induced plasticity across different cortical areas.
“Fmr1 mutant mice have a significant delay in the stabilization of dendritic spines and in the maturation of thalamocortical and corticocortical synapses 94-98 , defects associated with a temporal shift in the critical period for sensory-induced plasticity across different cortical areas 94,97,99-101 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [101]
Cites
FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism
Darnell, J. C., Van Driesche, S. J., Zhang, C., Hung, K. Y. S., Mele, A., Fraser, C. E., Stone, E. F., Chen, C., Fak, J. J., Chi, S. W., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.013 · Cited by 2,072 · see citing works
Translating developmental time across mammalian species
Clancy, B., Darlington, R. B., & Finlay, B. L. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00171-3 · Cited by 1,221 · see citing works
Long-term dendritic spine stability in the adult cortex
Grutzendler, J., Kasthuri, N., & Gan, W.-B. (2002) · Nature · doi:10.1038/nature01276 · Cited by 1,198 · see citing works
Abnormal dendritic spines in fragile X knockout mice: Maturation and pruning deficits
Comery, T. A., Harris, J. B., Willems, P. J., Oostra, B. A., Irwin, S. A., Weiler, I. J., & Greenough, W. T. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.10.5401 · Cited by 1,046 · see citing works
Tissue specific expression of FMR-1 provides evidence for a functional role in fragile X syndrome
Hinds, H. L., Ashley, C. T., Sutcliffe, J. S., Nelson, D. L., Warren, S. T., Housman, D. E., & Schalling, M. (1993) · Nature Genetics · doi:10.1038/ng0193-36 · Cited by 396 · see citing works
Delayed Stabilization of Dendritic Spines in Fragile X Mice
Cruz-Martin, A., Crespo, M., & Portera-Cailliau, C. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0577-10.2010 · Cited by 321 · see citing works
Irwin, S. A., Idupulapati, M., Gilbert, M. E., Harris, J. B., Chakravarti, A. B., Rogers, E. J., Crisostomo, R. A., Larsen, B. P., Mehta, A., Alcantara, C. J., et al. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10500 · Cited by 270 · see citing works
Circuit and Plasticity Defects in the Developing Somatosensory Cortex of<i>Fmr1</i>Knock-Out Mice
Bureau, I., Shepherd, G. M. G., & Svoboda, K. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1076-08.2008 · Cited by 201 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Autism spectrum disorder: neuropathology and animal models
Varghese, M., Keshav, N., Jacot-Descombes, S., Warda, T., Wicinski, B., Dickstein, D. L., Harony-Nicolas, H., De Rubeis, S., Drapeau, E., Buxbaum, J. D., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1736-4 · Cited by 536 · see citing works
The translation of translational control by FMRP: therapeutic targets for FXS
Darnell, J. C., & Klann, E. (2013) · Nature Neuroscience · doi:10.1038/nn.3379 · Cited by 491 · see citing works
Developmental timing and critical windows for the treatment of psychiatric disorders
Marín, O. (2016) · Nature Medicine · doi:10.1038/nm.4225 · Cited by 374 · see citing works
Henderson, C., Wijetunge, L., Kinoshita, M. N., Shumway, M., Hammond, R. S., Postma, F. R., Brynczka, C., Rush, R., Thomas, A., Paylor, R., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004218 · Cited by 249 · see citing works
Self-citationTill, S. M., Asiminas, A., Jackson, A. D., Katsanevaki, D., Barnes, S. A., Osterweil, E. K., Bear, M. F., Chattarji, S., Wood, E. R., Wyllie, D. J. A., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv299 · Cited by 109 · see citing works
Self-citationBarnes, S. A., Wijetunge, L. S., Jackson, A. D., Katsanevaki, D., Osterweil, E. K., Komiyama, N. H., Grant, S. G. N., Bear, M. F., Nägerl, U. V., Kind, P. C., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.1087-15.2015 · Cited by 84 · see citing works
Self-citationAsiminas, A., Jackson, A. D., Louros, S. R., Till, S. M., Spano, T., Dando, O., Bear, M. F., Chattarji, S., Hardingham, G. E., Osterweil, E. K., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aao0498 · Cited by 78 · see citing works
Self-citationKim, H., Kunz, P. A., Mooney, R., Philpot, B. D., & Smith, S. L. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.4204-15.2016 · Cited by 65 · see citing works
de Esch, C. E. F., van den Berg, W. E., Buijsen, R. A. M., Jaafar, I. A., Nieuwenhuizen-Bakker, I. M., Gasparini, F., Kushner, S. A., & Willemsen, R. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.12.021 · Cited by 45 · see citing works
Wang, Y., Sakano, H., Beebe, K., Brown, M. R., de Laat, R., Bothwell, M., Kulesza, R. J., & Rubel, E. W. (2014) · Journal of Comparative Neurology · doi:10.1002/cne.23520 · Cited by 40 · see citing works
- Authors
- Till, S. M., Wijetunge, L. S., Seidel, V. G., Harlow, E., Wright, A. K., Bagni, C., Contractor, A., Gillingwater, T. H., & Kind, P. C.
- Affiliations
- University of Edinburgh (GB)
- Northwestern University (US)
- University of Rome Tor Vergata (IT)
- Corresponding author
- Till, Sally M.
- Wijetunge, Lasani S.
- Kind, Peter C.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-02-09
- Volume
- 21
- Issue
- 10
- Pages
- 2143-2156
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2134620558
- Cited by
- 91
- References
- 8
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 9 · 2018: 6 · 2017: 5 · 2016: 11 · 2015: 11 · 2014: 8 · 2013: 15 · 2012: 4
- FWCI
- 7.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Lirias (submittedVersion)
- Funders
- Autism Speaks (AS1348)
- FRAXA Research Foundation
- University of Edinburgh
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Keywords
- fragile X syndrome, FMRP, Fmr1 knockout mice, primary somatosensory cortex, cortical maturation, dendritic spine morphology, glutamate receptor signaling, synaptic proteins, intellectual disability, neural circuits
- MeSH terms
- Animals, Disease Models, Animal, Fragile X Syndrome, Microscopy, Electron, RNA, Messenger, Somatosensory Cortex, Mice, Knockout, 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
