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Differentiation of Embryonic Stem Cells into Oligodendrocyte Precursors
Published on: May 19, 2010
Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon
N Tekki-Kessaris1, R Woodruff, A C Hall
1Wolfson Institute for Biomedical Research, The Cruciform Building, University College London, Gower Street, London WC1E 6AE, UK.
Development (Cambridge, England)
|August 9, 2001
Summary
Oligodendrocyte progenitor cells (OPCs) in the embryonic mouse forebrain develop similarly to those in the spinal cord. Sonic hedgehog (SHH) signaling is crucial for OPC development in the ventral forebrain and influences their migration and differentiation.
Area of Science:
- Developmental Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Oligodendrocyte progenitors (OLPs) are crucial for myelination in the central nervous system.
- In the caudal neural tube, OLP development is regulated by Sonic hedgehog (SHH) signaling.
- The developmental mechanisms of OLPs in the anterior neural tube are less understood.
Purpose of the Study:
- To investigate the origin and regulation of oligodendrocyte progenitors (OLPs) in the embryonic mouse forebrain.
- To determine the role of Sonic hedgehog (SHH) signaling in forebrain oligodendrogenesis.
- To compare OLP development in the anterior and caudal neural tube.
Main Methods:
- Analysis of platelet-derived growth factor alpha-receptor (PDGFRA) expression in embryonic mouse forebrain.
- Inhibition studies using cyclopamine to block hedgehog (HH) signaling.
- Gene expression analysis in wild-type and Nkx2.1 null mutant mice.
- In vitro culture of basal forebrain and neocortical progenitors.
Main Results:
- PDGFRA-expressing OLPs appear in the ventral forebrain neuroepithelium expressing SHH, PTCH, OLIG1, OLIG2, and SOX10.
- HH signaling inhibition with cyclopamine blocks OLP development in basal forebrain and neocortical cultures.
- OLP development is impaired in Nkx2.1 null mice, which lack ventral SHH expression.
Conclusions:
- Oligodendrogenesis in the embryonic mouse forebrain follows a pattern similar to the caudal neural tube.
- Sonic hedgehog (SHH) signaling is essential for the development of OLPs in the ventral telencephalon.
- SHH signaling may influence OLP development in the telencephalon, including the cerebral cortex.
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