Development of cortical interneurons

Most cortical interneurons are generated from progenitor cells located in the medial and caudal ganglionic eminences (MGE and CGE), which are anatomically defined and molecularly distinct compartments of the developing ventral forebrain. MGE progenitors produce parvalbumin- and somatostatin-positive cortical interneurons, while CGE progenitors produce cortical interneurons that label for calretinin and VIP. In contrast, progenitors in the neighboring lateral ganglionic eminence (LGE) produce interneurons destined for the granule and periglomerular layers of the olfactory bulb. The molecular mechanisms that underlie the differential production of cortical interneurons in the MGE and CGE, and the selective generation of olfactory bulb interneurons in the LGE, are presently unknown.

As a postdoctoral fellow, I found that migratory specificity of MGE and LGE cells is acquired from their progenitors, irrespective of their placement in the ventral forebrain. Subsequently, I uncovered novel molecular distinctions that further delineate LGE, MGE, and CGE progenitors, and identified the frontonasal mesenchyme as a potent modulator of ventral forebrain patterning. My lab is now exploring how cellular diversity amongst ventral forebrain progenitors is functionally translated into the unique migratory and differentiation programs of their post-mitotic progeny.

Currently, we are asking how newly identified MGE genes participate in the genesis, migration, and differentiation of MGE-derived cortical interneurons. One MGE-enriched gene, Map3K12 binding inhibitory protein 1 (Mbip), was originally identified as a negative regulator of c-Jun kinase (JNK) signal transduction, but its function in brain development has not yet been determined. In initial experiments we find that Mbip regulates neuronal migration, and accordingly, we are examining how Mbip, and more broadly, JNK signaling, contributes to cortical interneuron development.