HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Neurofibromatosis-1 regulation of neural stem cell proliferation and multilineage differentiation operates through distinct RAS effector pathways.

Abstract
Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disorder caused by impaired function of the neurofibromin RAS regulator. Using a combination of Nf1 genetically engineered mice and pharmacological/genetic inhibition approaches, we report that neurofibromin differentially controls neural stem cell (NSC) proliferation and multilineage differentiation through the selective use of the PI3K/AKT and RAF/MEK pathways. While PI3K/AKT governs neurofibromin-regulated NSC proliferation, multilineage differentiation is MEK-dependent. Moreover, whereas MEK-regulated multilineage differentiation requires Smad3-induced Jagged-1 expression and Notch activation, MEK/Smad3-regulated Hes1 induction is only responsible for astrocyte and neuronal differentiation. Collectively, these findings establish distinct roles for the RAS effector pathways in regulating brain NSC function.
AuthorsYi-Hsien Chen, Scott M Gianino, David H Gutmann
JournalGenes & development (Genes Dev) Vol. 29 Issue 16 Pg. 1677-82 (Aug 15 2015) ISSN: 1549-5477 [Electronic] United States
PMID26272820 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright© 2015 Chen et al.; Published by Cold Spring Harbor Laboratory Press.
Chemical References
  • Basic Helix-Loop-Helix Transcription Factors
  • Calcium-Binding Proteins
  • Hes1 protein, mouse
  • Homeodomain Proteins
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Receptors, Notch
  • Smad3 Protein
  • Serrate proteins
  • Phosphatidylinositol 3-Kinases
  • Oncogene Protein v-akt
  • Mitogen-Activated Protein Kinase Kinases
  • ras Proteins
Topics
  • Animals
  • Astrocytes (cytology)
  • Basic Helix-Loop-Helix Transcription Factors (metabolism)
  • Calcium-Binding Proteins (genetics)
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins (metabolism)
  • Intercellular Signaling Peptides and Proteins (genetics)
  • Membrane Proteins (genetics)
  • Mice
  • Mitogen-Activated Protein Kinase Kinases (metabolism)
  • Neural Stem Cells (cytology)
  • Neurofibromatosis 1 (genetics, metabolism)
  • Neurons (cytology)
  • Oncogene Protein v-akt (metabolism)
  • Phosphatidylinositol 3-Kinases (metabolism)
  • Receptors, Notch (metabolism)
  • Signal Transduction
  • Smad3 Protein (genetics, metabolism)
  • ras Proteins (genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: