Fig. 9. Progressive restrictions in homeodomain protein expression and the assignment of motor neuron columnar identity. (A) Profiles of HD and Olig2 protein expression in motor neuron progenitors and postmitotic motor neurons. Proteins shown in black designate expression in columnar neuronal subsets where expression is required for progression to a specific motor neuron columnar fate. Proteins shown in gray indicate expression in a particular subset of motor neurons under conditions in which these proteins do not influence motor neuron subtype determination, as assessed by gain- and loss-of-function studies. Late-stage motor neuron progenitors express Nkx6.1, MNR2, Lim3 and Olig2. Cell-cycle exit is accompanied by the extinction of Olig2 expression, the loss of Nkx6.1 from most motor neurons, and by the onset of expression of Isl1, Isl2 (not shown) and HB9. The emergence of medial MMC [MMC(m)] neuronal fate is accompanied by the persistence of expression of Isl1, HB9, MNR2 and Lim3, whereas lateral MMC [MMC(l)] and LMC fates are associated with the extinction of expression of Lim3 and MNR2. CT neuronal fate is associated with the extinction of MNR2, Lim3 and HB9 expression. Within the lateral MMC and LMC lineages, Lim3 represses motor neuron columnar fates independent of its ability to induce MNR2 expression, whereas within the CT lineage, the Lim3-mediated repression of CT identity is likely to be mediated by induction of Mnx class HD protein expression. (B) In dorsal neural progenitors, the repressor activity of MNR2 appears to induce motor neuron differentiation by repression of intermediate repressors (Xn) that function to repress expression of Lim3 and Isl1, proteins that when co-expressed have the capacity to direct motor neuron generation.