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Oligodendrocyte development and the onset of myelination in the human fetal brain
Open accessAbstract
Oligodendrocytes are cells that myelinate axons, providing saltatory conduction of action potentials and proper function of the central nervous system. Myelination begins prenatally in the human, and the sequence of oligodendrocyte development and the onset of myelination are not thoroughly investigated. This knowledge is important to better understand human diseases, such as periventricular leukomalacia, one of the leading causes of motor deficit in premature babies, and demyelinating disorders such as multiple sclerosis (MS). In this review we discuss the spatial and temporal progression of oligodendrocyte lineage characterized by the expression of specific markers and transcription factors in the human fetal brain from the early embryonic period (5 gestational weeks, gw) until midgestation (24 gw). Our in vitro evidence indicated that a subpopulation of human oligodendrocytes may have dorsal origin, from cortical radial glia cells, in addition to their ventral telencephalic origin. Furthermore, we demonstrated that the regulation of myelination in the human fetal brain includes positive and negative regulators. Chemokines, such as CXCL1, abundant in proliferative zones during brain development and in regions of remyelination in adult, are discussed in the view of their potential roles in stimulating oligodendrocyte development. Other signals are inhibitory and may include, but are not limited to, polysialic acid modification of the neural cell adhesion molecule on axons. Overall, important differences in temporal and spatial distribution and regulatory signals for oligodendrocyte differentiation exist between human and rodent brains. Those differences may underlie the unique susceptibility of humans to demyelinating diseases, such as MS.
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“In the fetal brain, it is probably caused by pre-myelination phases such as proliferation and maturation of oligodendrocyte and progenitor cells, the glia that form the myelin sheath (Jakovcevski et al., 2009).”
From Quantitative mapping of the brain’s structural connectivity using diffusion MRI tractography: A review (2022) · cites this paper as Jakovcevski et al., 2009
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Elia, J., Izaki, Y., Borreggine, K. L., Yost, O., Castro, A., Chang, C. Y., Ambrosini, A. P., Fels, S., Poddar, K., Rayfield, J., et al. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-823577-5.00012-x
Nejad, R. K. (2021) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-8737
Role of MeCP2 in oligodendrocyte lineage cells in Rett syndrome: review and inference
Zhang, Z., Li, P., & Chen, Y. (2023) · Ageing and Neurodegenerative Diseases · doi:10.20517/and.2023.13
Payette, K. (2023) · European Radiology · doi:10.1007/s00330-023-10450-4
Deficiência da vitamina b12 relacionada, fisiopatologicamente, com anemia megaloblástica e depressão
de Sousa, A. C., Vasconcelos, A. B., & dos Reis, D. K. D. S. S. (2024) · Caderno Pedagógico · doi:10.54033/cadpedv21n5-139
The molecular signature of Rett syndrome
Sangani, N. B. (2024) · Research Publications (Maastricht University) · doi:10.26481/dis.20240702ns
Cellular biology of the central nervous system
Leyendecker, J., Prasse, T., Karp, A., & Khaing, Z. Z. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95730-4.00016-0
Actions of Thyroid Hormones on Myelination
Bernal, J. (2024) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9789815274226124010015
Schuurmans, I. M. E., Mordelt, A., & de Witte, L. D. (2025) · Handbook of clinical neurology · doi:10.1016/b978-0-443-19104-6.00011-5
Morphology of Oligodendroglial Cells
Butt, A. M., Willis, A., Stevens, R., Hunter, I., & Nishiyama, A. (2025) · Advances in neurobiology · doi:10.1007/978-3-031-87919-7_5
The Clocks of Myelination: On Securing Accuracy of Neural Firing more than Velocity per se
Ferber, S. G. (2025) · Springer eBooks · doi:10.1007/978-3-031-89603-3_4
Evolution of glia in humans and other hominoids
Falcone, C. (2025) · Evolution of Nervous Systems · doi:10.1016/b978-0-443-27380-3.00065-8
Stem Cell Therapy for Neurological Disorders: From Bench to Bedside
Barbuti, P. A. (2014) · Springer eBooks · doi:10.1007/978-81-322-2110-4_4
Seeker, L. A., Bestard-Cuche, N., Jäkel, S., Kazakou, N.-L., Bøstrand, S. M. K., Wagstaff, L. J., Cholewa-Waclaw, J., Kilpatrick, A. M., van Bruggen, D., Kabbe, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26591057
Seeker, L. A., Bestard-Cuche, N., Jäkel, S., Kazakou, N.-L., Bøstrand, S. M. K., Wagstaff, L. J., Cholewa-Waclaw, J., Kilpatrick, A. M., van Bruggen, D., Kabbe, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26591051
Metadata
- Authors
- Jakovcevski, I.
- Venue
- Frontiers in Neuroanatomy
- Publisher
- Frontiers Media SA
- Published
- 2009
- Volume
- 3
- Pages
- 5-5
- ISSN
- 1662-5129 (ISSN-L)
- PMC
- PMC2694674
- OpenAlex
- W2018440098
- Cited by
- 323
- References
- 144
- Citations by year
- 2026: 14 · 2025: 17 · 2024: 31 · 2023: 30 · 2022: 26 · 2021: 34 · 2020: 22 · 2019: 17 · 2018: 22 · 2017: 9 · 2016: 12 · 2015: 13 · 2014: 20 · 2013: 23 · 2012: 8
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Neuroanatomy (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS041489)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Keywords
- oligodendrocyte development, myelination, human fetal brain, oligodendrocyte lineage, transcription factors, radial glia, polysialic acid, CD56, demyelinating disease, multiple sclerosis, periventricular leukomalacia, gestational development
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