Fig. 8. Model of transcriptional regulation for motoneuron-specific gene expression. (A) Progenitor cell domains (blue, green, red) in the ventral neural tube express specific combinations of transcription factors involved in cell fate specification (Briscoe et al., 2000). The floor plate (gray, FP) is shown. Progenitor cell factors from the p2 and p3 domains repress the general-activators of Hb9, providing direct evidence for the derepression model of gene regulation in the neural tube (Muhr et al., 2001) (reviewed by Lee and Pfaff, 2001). To achieve high level expression of Hb9 in motoneurons, however, enhancer factors Isl1, Lhx3 and NeuroM cooperate with general activators. (B) The spatial pattern of Hb9 expression in motoneurons is regulated by repressors (red) in non-motoneuron cells binding to dispersed sites. This report demonstrates that Irx3 and Nkx2.2 repress Hb9, but it remains unclear whether they function directly or indirectly. The postmitotic repression of Hb9 in non-motoneurons may be mediated by additional repressors (X^R). In differentiating motoneurons activators (green) bind to the enhancer (M250) and proximal 550 nucleotide segment of the promoter. Together this ensemble of specific and general proteins triggers high level transcription in motoneurons, which is modulated through negative feedback regulation by Hb9 protein.