BMP and FGF-2 regulate neurogenin-2 expression and the differentiation of sensory neurons and glia.

ABSTRACT

We have examined the effects of signaling molecules and Notch signaling on the mechanisms regulating neurogenin (ngn)-2 expression. This ngn-2 is a transcription factor that is essential for the specification of early differentiating sensory neurons in the dorsal root ganglia. In the presence of bone morphogenetic protein (BMP), anti-ngn-2-positive cells appeared in mouse trunk neural crest cell cultures, and they expressed Brn3, indicating that ngn-2-expressing cells are sensory neurons. These cells did not differentiate after fibroblast growth factor (FGF)-2 treatment or after Notch activation. The suppression of ngn-2 expression by FGF-2 was recovered by treatment with a Notch signaling inhibitor. Thus, FGF-2 may prevent ngn-2 expression through Notch activation. Whereas BMP-4 inhibited glial differentiation, FGF-2 promoted gliogenesis by means of Notch activation. Our data suggest that BMP and FGF-2 act as positive and negative regulators in ngn-2 expression, respectively, and that these signaling molecules regulate the differentiation of sensory neurons and glia.