Lhx2 specifies regional fate in Emx1 lineage of telencephalic progenitors generating cerebral cortex

Cerebral cortex is comprised of regions including six-layer neocortex and three-layer olfactory cortex generated by telencephalic progenitors of an Emx1 lineage. The mechanism specifying region-specific subpopulations within this lineage is unknown. We show in mouse that the LIM homeodomain transcription factor Lhx2, expressed in graded levels by progenitors, determines their regional identity and fate decisions to generate neocortex or olfactory cortex. Emx1-Cre deletion of Lhx2 at E10.5 refates progenitors to generate three-layer cortex phenocopying olfactory cortex rather than lateral neocortex. Progenitors do not generate ectopic olfactory cortex following Lhx2 deletion at E11.5. Thus, Lhx2 regulates a regional-fate decision by telencephalic progenitors during a critical period that closes as they differentiate from neuroepithelial cells to neuronogenic radial glia. “Exposure” of progenitors to Lhx2 may dictate their regional-fate decisions. These findings establish a genetic mechanism determining regional fate in the Emx1 lineage of telencephalic progenitors that generate cerebral cortex.