Cholera toxin regulates a signaling pathway critical for the expansion of neural stem cell cultures from the fetal and adult rodent brains.
BACKGROUND
New mechanisms that regulate neural stem cell (NSC) expansion will contribute to improved assay systems and the emerging regenerative approach that targets endogenous stem cells. Expanding knowledge on the control of stem cell self renewal will also lead to new approaches for targeting the stem cell population of cancers.


RESULTS
Here we show that Cholera toxin regulates two recently characterized NSC markers, the Tie2 receptor and the transcription factor Hes3, and promotes the expansion of NSCs in culture. Cholera toxin increases immunoreactivity for the Tie2 receptor and rapidly induces the nuclear localization of Hes3. This is followed by powerful cultured NSC expansion and induction of proliferation both in the presence and absence of mitogen.


CONCLUSIONS
Our data suggest a new cell biological mechanism that regulates the self renewal and differentiation properties of stem cells, providing a new logic to manipulate NSCs in the context of regenerative disease and cancer.
Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. AndreasTheotokis@gmail.com
Andreas
A
Androutsellis-Theotokis
Stuart
S
Walbridge
Deric M
DM
Park
Russell R
RR
Lonser
Ronald D G
RD
McKay
D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001921:Brain / Q000166:cytology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology*; D005333:Fetus / Q000166:cytology*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D042787:Receptor, TIE-2 / Q000378:metabolism; D012097:Repressor Proteins; D015398:Signal Transduction / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D002772:Cholera Toxin; D009419:Nerve Tissue Proteins; D042787:Receptor, TIE-2; D012097:Repressor Proteins; C411886:Hes3 protein, mouse