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Cited by 176Genetics and Neurodevelopmental DisordersNeurogenesis and neuroplasticity mechanismsFetal and Pediatric Neurological Disorders

Altered differentiation of neural stem cells in fragile X syndrome

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Castrén, Maija, Tervonen, Topi, Kärkkäinen, Virve, Heinonen, Seppo, Castrén, Eero, Larsson, Kim, Bakker, Cathy E., Oostra, Ben A. +1 more·2005·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0508995102PMC PMC1308923
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Abstract

Fragile X syndrome, a common form of inherited mental retardation, is caused by the absence of the fragile X mental retardation protein (FMRP) due to a mutation in the FMR1 gene. We investigated the differentiation of neural stem cells generated from the brains of fmr1- knockout (KO) mice and from postmortem tissue of a fragile X fetus. Mouse and human FMRP-deficient neurospheres generated more TuJ1-positive cells (3-fold and 5-fold, respectively) than the control neurospheres generated from normal mouse and human brains, and these cells showed morphological alterations with fewer and shorter neurites and a smaller cell body volume. The number of cells expressing glial fibrillary acidic protein and generated by these neurospheres was reduced because of increased apoptotic cell death. Furthermore, there was an increase in a population of cells with intense oscillatory Ca 2+ responses to neurotransmitters in differentiated cells lacking FMRP. In addition, the number of cells in a cohort of bromodeoxyuridine-labeled newborn cells was increased in the subventricular zone of the telencephalon of the fmr1 -KO mouse in vivo . These results demonstrate substantial alterations in the early maturation of FMRP-deficient neural stem cells in fragile X syndrome and in the fmr1 -KO mice.

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  1. [1]Turner, G., Webb, T., Wake, S. & Robinson, H. (1996) Am. J. Med. Genet. 64, 196-197. [DOI] [PubMed] [Google Scholar]
  2. [2]Jin, P. & Warren, S. T. (2000) Hum. Mol. Genet. 9, 901-908. [DOI] [PubMed] [Google Scholar]
  3. [3]Laggerbauer, B., Ostareck, D., Keidel, E. M., Ostareck-Lederer, A. & Fischer, U. (2001) Hum. Mol. Genet. 10, 329-338. [DOI] [PubMed] [Google Scholar]
  4. [4]Li, Z., Zhang, Y., Ku, L., Wilkinson, K. D., Warren, S. T. & Feng, Y. (2001) Nucleic Acids Res. 29, 2276-2283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. [5]Mazroui, R., Huot, M. E., Tremblay, S., Filion, C., Labelle, Y. & Khandjian, E. W. (2002) Hum. Mol. Genet. 11, 3007-3017. [DOI] [PubMed] [Google Scholar]
  6. [6]Miyashiro, K. Y., Beckel-Mitchener, A., Purk, T. P., Becker, K. G., Barret, T., Liu, L., Carbonetto, S., Weiler, I. J., Greenough, W. T. & Eberwine, J. (2003) Neuron 37, 417-431. [DOI] [PubMed] [Google Scholar]
  7. [7]Zalfa, F., Giorgi, M., Primerano, B., Moro, A., Di Penta, A., Reis, S., Oostra, B. & Bagni, C. (2003) Cell 112, 317-327. [DOI] [PubMed] [Google Scholar]
  8. [8]Bagni, C. & Greenough, W. T. (2005) Nat. Neurosci. Rev. 6, 376-397. [DOI] [PubMed] [Google Scholar]
  9. [9]Abitbol, M., Menini, C., Delezoide, A. L., Rhyner, T., Vekemans, M. & Mallet, J. (1993) Nat. Genet. 4, 147-153. [DOI] [PubMed] [Google Scholar]
  10. [10]Devys, D., Lutz, Y., Rouyer, N., Bellocq, J. P. & Mandel, J. L. (1993) Nat. Genet. 4, 335-340. [DOI] [PubMed] [Google Scholar]
  11. [11]Rudelli, R. D., Brown, W. T., Wisniewski, K., Jenkins, E. C., Laure-Kamionowska, M., Connell, F. & Wisniewski, H. M. (1985) Acta Neuropathol. 67, 289-295. [DOI] [PubMed] [Google Scholar]
  12. [12]Hinton, V. J., Brown, W. T., Wisniewski, K. & Rudelli, R. D. (1991) Am. J. Med. Genet. 41, 289-294. [DOI] [PubMed] [Google Scholar]
  13. [13]Wisniewski, K. E., Segan, S. M., Miezejeski, C. M., Sersen, E. A. & Rudelli, R. D. (1991) Am. J. Med. Genet. 38, 476-480. [DOI] [PubMed] [Google Scholar]
  14. [14]Irwin, S. A., Patel, B., Idupulapati, M., Harris, J. B., Crisostomo, R. A., Larsen, B. P., Kooy, F., Willems, P. J., Cras, P., Kozlowski, P. B., et al. (2001) Am. J. Med. Genet. 98, 161-167. [DOI] [PubMed] [Google Scholar]
  15. [15]The Dutch-Belgian Fragile X Consortium (1994) Cell 78, 23-33. [PubMed] [Google Scholar]
  16. [16]Musumeci, S. A., Bosco, P., Calabrese, G., Bakker, C., De Sarro, G. B., Elia, M., Ferri, R. & Oostra, B. A. (2000) Epilepsia 41, 19-23. [DOI] [PubMed] [Google Scholar]
  17. [17]Comery, T. A., Harris, J. B., Willems, P. J., Oostra, B. A., Irwin, S. A., Weiler, I. J. & Greenough, W. T. (1997) Proc. Natl. Acad. Sci. USA 94, 5401-5404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. [18]Braun, K. & Segal, M. (2000) Cereb. Cortex 10, 1045-1052. [DOI] [PubMed] [Google Scholar]
  19. [19]Irwin, S. A., Galvez, R. & Greenough, W. T. (2000) Cereb. Cortex 10, 1038-1044. [DOI] [PubMed] [Google Scholar]
  20. [20]Nimchinsky, E. A., Oberlander, A. M. & Svoboda, K. (2001) J. Neurosci. 21, 5139-5146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. [21]Galvez, R., Gopal, A. R. & Greenough, W. T. (2003) Brain Res. 971, 83-89. [DOI] [PubMed] [Google Scholar]
  22. [22]Huber, K. M., Gallagher, S. M., Warren, S. T. & Bear, M. F. (2002) Proc. Natl. Acad. Sci. USA 99, 7746-7750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. [23]Bahn, S., Mimmack, M., Ryan, M., Caldwell, M. A., Jauniaux, E., Starkey, M., Svendsen, C. N. & Emson, P. (2002) Lancet 359, 310-315. [DOI] [PubMed] [Google Scholar]
  24. [24]McKay, R. (1997) Science 276, 66-71. [DOI] [PubMed] [Google Scholar]
  25. [25]Clarke, D. L., Johansson, C. B., Wilbertz, J., Veress, B., Nilsson, E., Karlstrom, H., Lendahl, U. & Frisen, J. (2000) Science 288, 1660-1663. [DOI] [PubMed] [Google Scholar]
  26. [26]Ma, W., Maric, D., Li, B. S., Hu, Q., Andreadis, J. D., Grant, G. M., Liu, Q. Y., Shaffer, K. M., Chang, Y. H., Zhang, L., et al. (2000) Eur. J. Neurosci. 12, 1227-1240. [DOI] [PubMed] [Google Scholar]
  27. [27]Reynolds, B. A., Tetzlaff, W. & Weiss, S. (1992) J. Neurosci. 12, 4565-4574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. [28]Svendsen, C. N. & Caldwell, M. A. (2000) Prog. Brain Res. 127, 13-34. [DOI] [PubMed] [Google Scholar]
  29. [29]Ciccolini, F., Collins, T. J., Sudhoelter, J., Lipp, P., Berridge, M. J. & Bootman, M. D. (2003) J. Neurosci. 23, 103-111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. [30]Dolmetsch, R. E., Xu, K. & Lewis, R. S. (1998) Nature 392, 933-939. [DOI] [PubMed] [Google Scholar]
  31. [31]Vanderklish, P. W. & Edelman, G. M. (2002) Proc. Natl. Acad. Sci. USA 99, 1639-1644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. [32]Weiler, I. J., Spangler, C. C., Klintsova, A. Y., Grossman, A. W., Kim, S. H., Beraina-Anglade, V., Khaliq, H., de Vries, F. E., Lambers, F. A. E., Hatia, F., et al. (2004) Proc. Natl. Acad. Sci. USA 101, 17504-17509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. [33]Yan, Q. J., Rammal, M. & Bauchwitz, R. P. (2005) Neuropharmacology 49, 1053-1066. [DOI] [PubMed] [Google Scholar]
  34. [34]Bear, M. F., Huber, K. M. & Warren, S. T. (2004) Trends Neurosci. 27, 370-377. [DOI] [PubMed] [Google Scholar]
  35. [35]Taylor, C. W. & Thorn, P. (2001) Curr. Biol. 11, 352-355. [DOI] [PubMed] [Google Scholar]
  36. [36]Luo, X., Popov, S., Bera, A. K., Wilkie, T. M. & Muallem, S. (2001) Mol. Cell 7, 651-660. [DOI] [PubMed] [Google Scholar]
  37. [37]Tervonen, T., Åkerman, K. E. O., Oostra, B. A. & Castrén, M. (2004) Mol. Brain Res. 133, 162-165. [DOI] [PubMed] [Google Scholar]
  38. [38]Kooy, R. F., Reyniers, E., Verhoye, M., Sijbers, J., Bakker, C. E., Oostra, B. A., Willems, P. J. & Van Der Linden, A. (1999) Eur. J. Hum. Genet. 7, 526-532. [DOI] [PubMed] [Google Scholar]
  39. [39]Eliez, S., Blasey, C. M., Freund, L. S., Hastie, T. & Reiss, A. L. (2001) Brain 124, 1610-1618. [DOI] [PubMed] [Google Scholar]
  40. [40]Dong, W. K. & Greenough, W. T. (2004) Ment. Retard. Dev. Disabil. Res. Rev. 10, 85-90. [DOI] [PubMed] [Google Scholar]

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Authors
Castrén, M., Tervonen, T., Kärkkäinen, V., Heinonen, S., Castrén, E., Larsson, K., Bakker, C. E., Oostra, B. A., & Åkerman, K.
Affiliations
  • University of Helsinki (FI)
  • Neuroscience Center, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland; A. I. Virtanen Institute and Department of Obstetrics and Gynecology, University of Kuopio, P.O. Box 1627, 70211 Finland; and Department of Clinical Genetics, Erasmus Medical Center, Doctor Molewaterplein 50, 3000 DR Rotterdam, The Netherlands
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2005-11-28
Volume
102
Issue
49
Pages
17834-17839
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0508995102
PMC
PMC1308923
OpenAlex
W2014081519
Cited by
176
References
41
Citations by year
2026: 3 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 2 · 2021: 5 · 2020: 12 · 2019: 12 · 2018: 6 · 2017: 11 · 2016: 12 · 2015: 13 · 2014: 21 · 2013: 15 · 2012: 13
FWCI
2.35
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
Keywords
fragile X syndrome, FMRP, neural stem cells, neurospheres, neuronal differentiation, Fmr1 knockout mice, neurite morphology, glial fibrillary acidic protein, apoptosis, calcium oscillations, subventricular zone, telencephalon, neurogenesis, intellectual disability
MeSH terms
Animals, Calcium, Cell Differentiation, Cells, Cultured, Fragile X Syndrome, Neurons, Stem Cells, Mice, Knockout, Mice, Fragile X Messenger Ribonucleoprotein 1, Fragile X Mental Retardation Protein

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