Neurons or glia? Can SHP2 know it all?
Normal development of the nervous system relies on the spatially and temporally well-controlled differentiation of neurons and glia. Here, we discuss the intra- and extracellular molecular mechanisms that underlie the sequential genesis of neurons and glia, emphasizing recent studies describing the role of a signaling molecule, the tyrosine phosphatase SHP2, in normal brain development. Activation of SHP2 simultaneously enhances downstream activation of the MEK-ERK pathway, which subsequently promotes neurogenesis, while inhibiting the JAK-STAT pathway, which is critical for astroglial differentiation. Mutations in SHP2 that increase its tyrosine phosphatase activity cause a mental retardation-related disorder, Noonan syndrome. An imbalance in neurogenesis versus gliogenesis due to SHP2 mutations may contribute to Noonan syndrome.
Coskun
Volkan
V
Mental Retardation Research Center, Department of Molecular and Medical Pharmacology, Neuropsychiatric Institute, David Geffen School of Medicine, University of California Los Angeles, 635 Charles E. Young Drive South, Los Angeles, CA 90095, USA.
Zhao
Jing
J
Sun
Yi E
YE
D000818:Animals; D049109:Cell Proliferation; D006801:Humans; D009457:Neuroglia / Q000201:enzymology*; D009474:Neurons / Q000201:enzymology*; D009634:Noonan Syndrome / Q000201:enzymology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism*; D013234:Stem Cells / Q000201:enzymology
D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11