The in vitro differentiation of mouse embryonic stem cells (mESCs) into forebrain neuronal types recapitulates many aspects of in vivo neural development. Directed in vitro differentiation of human embryonic stem cells (hESCs) into neuronal subtypes has been harder to achieve but, on p. 4056, Li and colleagues report that, in the absence of known morphogens, hESCs differentiate into dorsal telencephalic progenitors. They show that endogenous Wnt signalling drives this differentiation through the upregulation of truncated GLI3, a repressor of sonic hedgehog (SHH). High concentrations of SHH or inhibition of Wnt signalling, they report, almost completely convert the dorsal progenitors to ventral progenitors, in part by regulating the expression of active and repressive forms of GLI3. Finally, they show that these dorsal and ventral precursors differentiate into functional glutamatergic and GABAergic neurons, respectively. Interestingly, these results suggest that, although hESCs generate dorsal telencephalic cells in the absence of exogenous morphogens, whereas mESCs generate ventral precursors, a similar molecular mechanism controls dorsal-ventral telencephalic patterning in mice and humans.
Stem cell neuronal differentiation in mice and men
Stem cell neuronal differentiation in mice and men. Development 1 December 2009; 136 (23): e2301. doi:
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