Figure 13.

Schematic representation of our proposed model for the role of Prox1 in p2/pMN boundary specification. During the early stages of ventral spinal cord development a subset of naive progenitors are generated that will later give rise to either V2 interneurons or MNs (Wu et al., 2006; Dessaud et al., 2007, 2008, 2010; J. A. Chen et al., 2011). A cross-inhibitory transcriptional regulation between Prox1 and Olig2 determines the V2 or MN cell fate by refining the p2/pMN boundary. In the dorsal-most progenitors, Prox1 expression is sustained to suppress Olig2, inhibit MN generation, and promote V2 identity (Chx10+, Gata2+, Gata3+, and ventral Lhx1/5+). Conversely, in the ventral-most progenitors, Olig2 expression is sustained to repress Prox1, block V2 identity, and allow MN specification (ChAT+). Consistent with this model, upon shRNA-mediated knock-down of Prox1 (shProx1), its inhibitory effect on Olig2 is alleviated and the expression domain of Olig2 (pMN) is dorsally expanded at the expense of p2.