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Cited by 80Genetics and Neurodevelopmental DisordersNeurogenesis and neuroplasticity mechanismsNeuroscience and Neuropharmacology Research

Fragile X mental retardation protein regulates new neuron differentiation in the adult olfactory bulb

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Scotto-Lomassese, Sophie, Nissant, Antoine, Mota, Tatiana, Néant-Féry, Marie, Oostra, Ben A., Greer, Charles A., Lledo, Pierre-Marie, Trembleau, Alain +1 more·2011·The Journal of Neuroscience
DOI 10.1523/jneurosci.5514-10.2011PMC PMC3682409
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Abstract

The fragile X mental retardation protein (FMRP) is an RNA-binding protein essential for multiple aspects of neuronal mRNA metabolism. Its absence leads to the fragile X syndrome, the most prevalent genetic form of mental retardation. The anatomical landmark of the disease, also present in the Fmr1 knock-out (KO) mice, is the hyperabundance of immature-looking lengthened dendritic spines. We used the well known continuous production of adult-born granule cells (GCs) in the mouse olfactory bulb (OB) to analyze the consequences of Fmrp loss on the differentiation of GCs. Morphological analysis of GCs in the Fmr1 KO mice showed an increase in spine density without a change in spine length. We developed an RNA interference strategy to cell-autonomously mutate Fmr1 in a wild-type OB network. Mutated GCs displayed an increase in spine density and spine length. Detailed analysis of the spines through immunohistochemistry, electron microscopy, and electrophysiology surprisingly showed that, despite these abnormalities, spines receive normal glutamatergic synapses, and thus that mutated adult-born neurons are synaptically integrated into the OB circuitry. Time-course analysis of the spine defects showed that Fmrp cell-autonomously downregulates the level and rate of spine production and limits their overgrowth. Finally, we report that Fmrp does not regulate dendritogenesis in standard conditions but is necessary for activity-dependent dendritic remodeling. Overall, our study of Fmrp in the context of adult neurogenesis has enabled us to carry out a precise dissection of the role of Fmrp in neuronal differentiation and underscores its pleiotropic involvement in both spinogenesis and dendritogenesis.

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Crossref · 10.1523/jneurosci.5514-10.2011

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  • In Fmr1-null mice, the density of spines in control ShScr-infected neurons was significantly increased to 0.66±0.06 spines/μm compared with ShScr-infected neurons in normal mice.

    “In Fmr1-null mice (Fig. 2C,F), the density of spines in control ShScr-infected neurons was significantly increased to 0.66±0.06 spines/µm compared with ShScr-infected neurons in normal mice (Fig. 2C,F), as we already described (Scotto-Lomassese et al., 2011)”

    From New insights into the regulatory function of CYFIP1 in the context of WAVE- and FMRP-containing complexes (2017) · cites this paper as Scotto-Lomassese et al., 2011

    The Results section, “Newborn GCs in Fmr1 KO mice display increased spine density” (page unavailable), reports significantly greater spine density in knockout than wild-type mice. It reports a 26% increase after GFP-lentivirus injection, however, not a comparison of ShScr-infected neurons, and our copy does not give the claimed value of 0.66 ± 0.06 spines/µm. The paper uses a different control shRNA, shNeg, in a separate experiment. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The study used an already validated ex vivo system.

    “All these considerations support the use of an already validated ex vivo system (Scotto-Lomassese et al., 2011; Daroles et al., 2015), as we used here.”

    From New insights into the regulatory function of CYFIP1 in the context of WAVE- and FMRP-containing complexes (2017) · cites this paper as Scotto-Lomassese et al., 2011

    The Electrophysiology methods (page unavailable) describe recordings from dissected olfactory-bulb slices, supporting that the study used an ex vivo preparation. The copy does not say that this preparation was validated as the ex vivo system cited in the sentence. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

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Authors
Scotto-Lomassese, S., Nissant, A., Mota, T., Néant-Féry, M., Oostra, B. A., Greer, C. A., Lledo, P.-M., Trembleau, A., & Caillé, I.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Erasmus MC (NL)
  • Yale University (US)
Corresponding author
Caillé, Isabelle
ORCID
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2011-02-09
Volume
31
Issue
6
Pages
2205-2215
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.5514-10.2011
PMC
PMC3682409
OpenAlex
W2061959727
Cited by
80
References
12
Citations by year
2025: 1 · 2024: 5 · 2023: 5 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 5 · 2018: 7 · 2017: 8 · 2016: 8 · 2015: 5 · 2014: 6 · 2013: 9 · 2012: 6
FWCI
5.59
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Funders
  • Agence Nationale de la Recherche
  • Institut National de la Santé et de la Recherche Médicale
  • Centre National de la Recherche Scientifique
  • École des Neurosciences Paris Île de France
  • National Institute on Deafness and Other Communication Disorders (R01DC000210)
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, adult neurogenesis, olfactory bulb, granule cells, dendritic spines, dendritogenesis, dendritic remodeling, Fmr1 knockout mice, RNA interference, synaptic integration, fragile X syndrome, neuronal differentiation
MeSH terms
Analysis of Variance, Animals, Cell Differentiation, Dendrites, Male, Mice, Inbred C57BL, Mutation, Neurons, Olfactory Bulb, Synapses, Time Factors, Mice, Knockout, Patch-Clamp Techniques, Excitatory Postsynaptic Potentials, RNA, Small Interfering, Microscopy, Electron, Transmission, Dendritic Spines, Green Fluorescent Proteins, Mice, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1, Neurogenesis

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