Basic helix-loop-helix (bHLH) transcription factors are known to function d
uring mammalian neurogenesis, Here we show that transient transfection of v
ectors expressing neuroD2, MASH1, ngn1 or related neural bHLH proteins, wit
h their putative dimerization partner E12, can convert mouse P19 embryonal
carcinoma cells into differentiated neurons. Transfected cells express nume
rous neuron-specific proteins, adopt a neuronal morphology and are electric
ally excitable. Thus, the expression of neural bHLH proteins is sufficient
to confer a neuronal fate on uncommitted mammalian cells. Neuronal differen
tiation of transfected cells is preceded by elevated expression of the cycl
in-dependent kinase inhibitor p27(Kip1) and cell cycle withdrawal, This dem
onstrates that the bHLH proteins can link neuronal differentiation to withd
rawal from the cell cycle, possibly by activating the expression of p27(Kip
1), The ability to generate mammalian neurons by transient expression of ne
ural bHLH proteins should create new opportunities for studying neurogenesi
s and devising neural repair strategies.