Fig. 8. Postulated genetic interactions during cranial motoneuron differentiation in the ventral hindbrain and upon misexpression of Phox2b in the dorsolateral neural tube. (A) Within the bm/vm progenitor domain, Phox2b in combination with Nkx2.2 drives Mash1 expression, which in turn promotes generic neuronal differentiation. Repression of Hes and Id gene expression by Phox2b may be necessary to overcome a negative feedback on neuronal differentiation triggered by Mash1. In the progenitor domain, Nkx2.2 and Phox2b repress Pax6 and Olig2, which can be supposed to inhibit bm/vm specification. Phox2b is postulated to boost expression of the Nkx6 genes that are required for proper development of bm/vm neurons. The inhibitory interaction between Pax6 and Phox2b is reciprocal. (B) Upon misexpression in the dorsolateral spinal cord and caudal hindbrain, Phox2b is postulated to cooperate with an unknown HD factor (X) to upregulate Ngn2, which in turn drives pan-neuronal differentiation. By boosting expression of Hes5 and Id2, Ngn2 triggers a negative feedback loop that is relieved by Phox2b. In addition, Phox2b directs a bm/vm fate, in part by repressing Pax6 and Olig2, which are not permissive for this fate, and by upregulating expression of the Nkx6 genes, which are compatible with it. In A,B, the positive autoregulation of Phox2b has been omitted for clarity.

Return to article