The DOI matches its Crossref record; 30 of the 31 references it cites were found in a registry or an index.
FMRP regulates the transition from radial glial cells to intermediate progenitor cells during neocortical development.
Open accessAbstract
During vertebrate cortical neurogenesis, radial glial cells (RGCs) serve as neural stem cells that generate neurons directly or indirectly through intermediate progenitor cells (IPCs). The transition from RGCs to IPCs is a key step in determining overall neuronal production and may underlie evolutionary expansion of the cerebral cortex. Here we show that this transition is controlled by fragile X mental retardation protein (FMRP), an RNA-binding protein whose deficiency causes fragile X syndrome. Analysis of mouse embryos electroporated with FMRP small hairpin RNA and knock-out mouse embryos lacking FMRP reveals that specific loss of FMRP causes depletion of neocortical RGCs due to an RGC-to-IPC cell fate change. The RGC depletion is associated with altered F-actin organization and can be largely rescued by overexpressing profilin 1 (Pfn1), a core actin regulatory protein promoting F-actin formation. Our data suggest that FMRP suppresses the transition from RGCs to IPCs during neocortical development by an actin-dependent mechanism.
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“Loss of FMRP-mediated translational control results in altered cell fate specification during early neural development (Tervonen et al., 2009; Saffary and Xie, 2011; Utami et al., 2020).”
From Astrocytes in fragile X syndrome (2024) · cites this paper as Saffary and Xie, 2011
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1 retracted
Fasano, C. A., Dimos, J. T., Ivanova, N. B., Lowry, N. A., Lemischka, I. R., & Temple, S. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.04.001 · Cited by 308 · cited 3×
“…have shown that functional compensation commonly occurs during development when the gene is constitutively deleted but not when the protein is acutely lost or inhibited (Deuel et al., 2006; Koizumi et al., 2006; Fasano et al., 2007; Satyanarayana and cortical neurogenesis than at later stages.”
BackgroundRetractedThe Glial Nature of Embryonic and Adult Neural Stem Cells
Kriegstein, A., & Alvarez-Buylla, A. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135600 · Cited by 2,475 · cited 6×
“The RGC-to-IPC transition, a key step in neuronal production from RGCs, may underlie the evolutionary expansion of the cerebral cortex (Fish et al., 2008; Kriegstein and Alvarez-Buylla, 2009).”
BackgroundInfluentialLifeact: a versatile marker to visualize F-actin
Riedl, J., Crevenna, A. H., Kessenbrock, K., Yu, J. H., Neukirchen, D., Bista, M., Bradke, F., Jenne, D., Holak, T. A., Werb, Z., et al. (2008) · Nature Methods · doi:10.1038/nmeth.1220 · Cited by 2,189 · cited 3×
“To overcome this problem, we used Lifeact-EGFP (Riedl et al., 2008, 2010), a fusion protein comprised of an F-actin binding domain and EGFP, to visualize the ring-like F-actin structure in transfected RGCs (Fig.”
BackgroundMethodFragile X Syndrome: Loss of Local mRNA Regulation Alters Synaptic Development and Function
Bassell, G. J., & Warren, S. T. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.004 · Cited by 1,051 · cited 6×
“The I304N mutation impairs the association of FMRP with RNA (Bassell and Warren, 2008) and renders the protein a null mutant (Zang et al., 2009).”
BackgroundInfluentialMammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms
Satyanarayana, A., & Kaldis, P. (2009) · Oncogene · doi:10.1038/onc.2009.170 · Cited by 800 · cited 4×
“Moreover, potential function of FMRP in RGCs may be masked in Fmr1 knock-out embryos by compensation, which often occurs in constitutive knock-out mice (Deuel et al., 2006; Koizumi et al., 2006; Fasano et al., 2007; Satyanarayana and Kaldis, 2009).”
BackgroundResultInfluentialGal, J. S., Morozov, Y. M., Ayoub, A. E., Chatterjee, M., RAKIC, P. T., & Haydar, T. F. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4499-05.2006 · Cited by 358 · cited 2×
“Immediately following mCherry electroporation, EGFP should label cells with reduced levels of FMRP, because FMRP shRNA was coelectroporated with pCAX-EGFP 2 d before, and mCherry should label RGCs because in utero electroporation leads to specific transfection of RGCs (Gal et al., 2006).”
MethodThe fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2.
Zhang, Y., O'Connor, J. P., Siomi, M. C., Srinivasan, S., Dutra, A., Nussbaum, R. L., & Dreyfuss, G. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00220.x · Cited by 337 · cited 1×
“These three proteins have similar domain structures and interact with each other (Zhang et al., 1995).”
BackgroundLifeact mice for studying F-actin dynamics
Riedl, J., Flynn, K. C., Raducanu, A., Gärtner, F. C., Beck, G., Bösl, M. R., Bradke, F., Maßberg, S., Aszódi, A., Sixt, M., et al. (2010) · Nature Methods · doi:10.1038/nmeth0310-168 · Cited by 333 · cited 3×
“To overcome this problem, we used Lifeact-EGFP (Riedl et al., 2008, 2010), a fusion protein comprised of an F-actin binding domain and EGFP, to visualize the ring-like F-actin structure in transfected RGCs (Fig.”
BackgroundMethodSchenck, A., Bardoni, B., Langmann, C., Harden, N., Mandel, J.-L., & Giangrande, A. (2003) · Neuron · doi:10.1016/s0896-6273(03)00354-4 · Cited by 316 · cited 2×
“FMRP maintains the RGC pool by regulating the actin cytoskeleton Previous studies indicate that FMRP may regulate neuronal function by an actin-dependent mechanism (Schenck et al., 2003; Reeve et al., 2005).”
BackgroundDeuel, T. A., Liu, J. S.-H., Corbo, J. C., Yoo, S.-Y., Rorke-Adams, L. B., & Walsh, C. A. (2006) · Neuron · doi:10.1016/j.neuron.2005.10.038 · Cited by 291 · cited 5×
“Moreover, potential function of FMRP in RGCs may be masked in Fmr1 knock-out embryos by compensation, which often occurs in constitutive knock-out mice (Deuel et al., 2006; Koizumi et al., 2006; Fasano et al., 2007; Satyanarayana and Kaldis, 2009).”
BackgroundResultInfluential
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Items 101–103 of 103
The Role of RNA-protein Granules in Neurodevelopment
Illarionova, N. B., & Moshkin, M. P. (2026) · Biology Bulletin Reviews · doi:10.1134/s2079086426700027
“Normally, FMRP prevents the premature translation of mRNA, which is critical for proper neu-rodevelopment, regulating RGCs differentiation, as well as influencing neuron morphology (Dictenberg et al., 2008; Lai et al., 2020; Saffary and Xie, 2011).”
Blumenthal, K. H., McLellan, J., & de Water, J. V. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1794161
“…) gene observed in Fragile-X Syndrome and ASD have been found to lead to increased IPC production and depleted levels of RGCs, as well as delayed transition of neurons into a bipolar morphology, which can be linked to subsequent irregular neuronal migration and impaired neuronal networks (62, 63).”
Couce-Iglesias, M., Oliani, E., Kerridge, R., Mutschler, F., Valdes, D. S., Welter, A. S., Lukaszewska‐McGreal, B., Meierhofer, D., Imami, K., Fornasiero, E. F., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.21.753234
“…increasing protein stability may support the accumulation of total protein despite decreasing transcripts and heavy protein output, which is characteristic of genes that pattern cortical areas like Nr2f1 (Coup-tf1) 29 and regulate neuronal differentiation and synaptogenesis like Fmrp (Fmr1) 30,31 .”
Metadata
- Authors
- Saffary, R., & Xie, Z.
- Affiliations
- Boston Medical Center (US)
- Boston University (US)
- Corresponding author
- Xie, Zhigang
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-01-26
- Volume
- 31
- Issue
- 4
- Pages
- 1427-1439
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6623593
- OpenAlex
- W2082366834
- Cited by
- 103
- References
- 31
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 1 · 2022: 9 · 2021: 6 · 2020: 9 · 2019: 11 · 2018: 5 · 2017: 13 · 2016: 8 · 2015: 3 · 2014: 10 · 2013: 11 · 2012: 4
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Keywords
- FMRP, fragile X syndrome, radial glia, intermediate progenitor cells, cortical neurogenesis, neocortex development, cell fate transitions, actin cytoskeleton, F-actin organization, profilin-1, RNA-binding proteins, cerebral cortex evolution
- MeSH terms
- Actins, Animals, Neuroglia, Mice, Knockout, Neocortex, RNA, Small Interfering, Mice, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1, Neurogenesis, Neural Stem Cells
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