Olig bHLH proteins interact with homeodomain proteins to regulate cell fate acquisition in progenitors of the ventral neural tube

Background: Organizing signals such as Sonic hedgehog are thought to specif y neuronal subtype identity by regulating the expression of homeodomain pro teins in progenitors of the embryonic neural tube. One of these, Nkx2.2, is necessary and sufficient for the development of V3 interneurons. Results: We report that Olig genes, encoding basic helix-loop-helix (bHLH) proteins, are expressed in a subset of Nkx2.2 progenitors before the establ ishment of interneurons and oligodendroglial precursors. Gain-of-function a nalysis in transgenic mouse embryos indicates that Olig genes specifically inhibit the establishment of Sim1-expressing V3 interneurons. Moreover, coe xpression of Olig2 with Nkx2.2 in the chick neural tube generated cells exp ressing Sox10, a marker of oligodendroglial precursors. Colocalization of O lig and Nkx2.2 proteins at the dorsal extent of the Nkx2.2 expression domai n is consistent with regulatory interactions that define the potential of p rogenitor cells in the border region. Conclusions: Interactions between homeodomain and Olig bHLH proteins eviden tly regulate neural cell fate acquisition and diversification in the ventra l neural tube. In particular, interactions between Olig and Nkx2.2 proteins inhibit V3 interneuron development and promote the formation of alternate cell types, including those expressing Sox10.