Pax6 regulates Tbr1 and Tbr2 expressions in olfactory bulb mitral cells.

Tracking olfactory bulb mitral cell development with BrdU labeling, we find that mitral cells are generated from Pax6+ radial glial cells in the ventricular zone of the embryonic olfactory bulb. Unlike cortical projection neurons, postmitotic mitral cell precursors express both Tbr1 and Tbr2. Our tracking experiments revealed that down-regulation of Pax6 preceded up-regulation of Tbrs, and that Tbr1 emerged earlier than Tbr2. Using in utero electroporation, we also show that Pax6 negatively regulates the expression of Tbr1 and Tbr2 in postmitotic mitral cell precursors. Exogenous expression of Pax6 in embryonic olfactory bulb postmitotic precursors decreased the number of cells that progressed to a mitral cell fate. In contrast, exogenous expression of Pax6 resulted in an increase of GABAergic and/or dopaminergic interneurons. These results indicate that Pax6 is a regulator of fate determination of precursor cells.