Cortical neurogenesis in fragile X syndrome
Abstract
The absence of fragile X mental retardation 1 protein (FMRP) results in fragile X syndrome (FXS) that is a common cause of intellectual disability and a variant of autism spectrum disorder. There is evidence that FMRP is involved in neurogenesis. FMRP is widely expressed throughout the embryonic brain development and its expression levels increases during neuronal differentiation. Cortical neural progenitors propagated from human fetal FXS brain show expression changes of genes which encode components of intracellular signal transduction cascades, including receptors, second messengers, and transduction factors. The absence of functional FMRP enhances transition of radial glia to intermediate progenitor cells. Radial glial cells provide scaffolding for migrating neurons and express functional receptors for metabotropic glutamate receptors. The absence of FMRP results in alterations of neuronal differentiation and migration, which contribute to developmental changes in brain structure and function in FXS. Here, cortical neurogenesis in FXS is reviewed and the putative contribution of brain-derived neurotrophic factor to defects of FXS neurogenesis is discussed.
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The early reduction in parvalbumin cell number may occur because of abnormal interneuron differentiation and migration during embryonic development.
“This early reduction in the number of PV cells may occur due to abnormal interneuron differentiation and migration during embryonic development (Castrén et al. 2005;reviewed in Castrén 2016).”
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- Authors
- Castrén, M. L.
- Affiliations
- University of Helsinki (FI)
- Corresponding author
- Castrén, Maija L
- ORCID
- Castrén, Maija L
- Venue
- Frontiers in Bioscience
- Publisher
- IMR Press
- Published
- 2016
- Volume
- 8
- Issue
- 1
- Pages
- 160-168
- ISSN
- 1944-7906 (ISSN-L)
- 1945-0516
- 1945-0524
- DOI
- 10.2741/s455
- OpenAlex
- W2342472421
- Cited by
- 24
- References
- 0
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 2 · 2015: 1
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Frontiers in Bioscience-Scholar (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Päivikki ja Sakari Sohlbergin Säätiö
- 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, cortical neurogenesis, neural progenitor cells, radial glia, intermediate progenitor cells, neuronal migration, neuronal differentiation, metabotropic glutamate receptors, signal transduction, brain-derived neurotrophic factor, intellectual disability, autism spectrum disorder
- MeSH terms
- Autism Spectrum Disorder, Animals, Cell Movement, Cerebral Cortex, Fragile X Syndrome, Humans, Stem Cells, Signal Transduction, Brain-Derived Neurotrophic Factor, Fragile X Messenger Ribonucleoprotein 1, Neurogenesis, Neural Stem Cells
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