Related Experiment Video
Updated: Feb 19, 2026
08:57
Author Spotlight: Genetically Engineered Mouse Models and Pathological Characterization of Neurofibromatosis Type 1 Associated Tumors
Published on: May 17, 2024
2.7K
Neurofibromin, the Neurofibromatosis Type 1 Ras-GAP, Is Required for Appropriate P0 Expression and Myelination
Thorsten Rosenbaum1, Haesun A Kim1, Ying L Boissy1
1Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati Medical School, P.O. Box 670521, Cincinnati, Ohio 45267-0521, USA.
Annals of the New York Academy of Sciences
|November 1, 2017
Summary
Neurofibromatosis type 1 (NF1) deficiency impairs myelination by affecting not only Schwann cells but also neurons and fibroblasts. This suggests NF1 signaling is crucial in multiple cell types for proper myelin formation.
Area of Science:
- Neuroscience
- Cell Biology
- Genetics
Background:
- Neurofibromin, the NF1 gene product, regulates the Ras signaling pathway.
- Loss of NF1 in Schwann cells leads to increased expression of the P0 myelin glycoprotein.
- Ras signaling is implicated in P0 upregulation in NF1-deficient cells.
Purpose of the Study:
- To investigate the role of NF1 in myelin formation by Schwann cells.
- To determine if NF1-dependent signaling in neurons and/or fibroblasts is necessary for myelination.
Main Methods:
- Culturing Nf1-deficient Schwann cells with normal neurons.
- Expressing v-Ras in cultured Schwann cells.
- Utilizing organotypic cultures of neurons, Schwann cells, and fibroblasts lacking neurofibromin.
Main Results:
- Nf1-deficient or v-Ras-expressing Schwann cells showed no significant changes in myelin formation when cultured with normal neurons.
- Myelination was dramatically reduced in organotypic cultures lacking neurofibromin in neurons, Schwann cells, and fibroblasts.
Conclusions:
- NF1 signaling in Schwann cells alone is insufficient for normal myelination.
- NF1-dependent signaling cascades in neurons and/or fibroblasts, in addition to Schwann cells, are essential for proper myelination.
More Related Videos
Related Concept Videos
02:38The Ras Gene
7.4K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Ras is a...
7.4K
01:24Small GTPases - Ras and Rho
5.5K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
5.5K
02:23Abnormal Proliferation
5.3K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.3K
01:19Interactions Between Signaling Pathways
7.4K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.4K
01:14Rab Proteins
5.2K
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
5.2K