During development, the secreted molecule Sonic Hedgehog (Shh) is required for lineage specification and proliferation of oligodendrocyte progenitors (OLPs), which are the glia cells responsible for the myelination of axons in the central nervous system (CNS). Shh signaling has been implicated in controlling both the generation of oligodendrocytes (OLGs) during embryonic development and their production in adulthood. Although, some evidence points to a role of Shh signaling in OLG development, its involvement in OLG differentiation remains to be fully determined. The objective of this study was to assess whether Shh signaling is involved in OLG differentiation after neural stem cell commitment to the OLG lineage. To address these questions, we manipulated Shh signaling using cyclopamine, a potent inhibitor of Shh signaling activator Smoothened (Smo), alone or combined with the agonist SAG in OLG primary cultures and assessed expression of myelin-specific markers. We found that inactivation of Shh signaling caused a dose-dependent decrease in myelin basic protein (MBP) and myelin associated glycoprotein (MAG) in differentiating OLGs. Co-treatment of the cells with SAG reversed the inhibitory effect of cyclopamine on both myelin-specific protein levels and morphological changes associated with it. Further experiments are required to elucidate the molecular mechanism by which Shh signaling regulates OLG differentiation.
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http://dx.doi.org/10.1007/s11064-016-2061-3 | DOI Listing |
Biofactors
January 2025
College of Pharmacy, Sunchon National University, Sunchon, Republic of Korea.
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View Article and Find Full Text PDFBone Res
January 2025
Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, Jiangsu Province, China.
Plp1-lineage Schwann cells (SCs) of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing, and the abnormal plasticity of SCs would jeopardize the bone regeneration. However, how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood. Here, by employing single-cell transcriptional profiling combined with lineage-specific tracing models, we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury.
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January 2025
Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address:
Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Developmental and Regenerative Biology, Medical Research Institute, Institute of Science Tokyo, Tokyo 113-8510, Japan.
The eye primordium of vertebrates initially forms exactly at the side of the head. Later, the eyeball architecture is tuned to see ahead with better visual acuity, but its molecular basis is unknown. The position of both eyes in the face alters in patients with holoprosencephaly due to () mutations that disturb the development of the ventral midline of the neural tube.
View Article and Find Full Text PDFAntioxidants (Basel)
January 2025
Energy & Memory, Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, F-75006 Paris, France.
Medulloblastoma (MB) is the most common malignant brain tumor in children, typically arising during infancy and childhood. Despite multimodal therapies achieving a response rate of 70% in children older than 3 years, treatment remains challenging. Ferroptosis, a form of regulated cell death, can be induced in medulloblastoma cells in vitro using erastin or RSL3.
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