Emx1-Lineage Progenitors Differentially Contribute to Neural Diversity in the Striatum and Amygdala

In the developing mammalian basal telencephalon, neural progenitors from the subpallium generate the majority of inhibitory medium spiny neurons (MSNs) in the striatum, while both pallial-and subpallial-derived progenitors contribute to excitatory and inhibitory neuronal diversity in the amygdala. Using a combination of approaches, including genetic fate mapping, cell birth dating, cell migration assays, and electrophysiology, we find that cells derived from the Emx1 lineage contribute to two distinct neuronal populations in the mature basal forebrain: inhibitory MSNs in the striatum and functionally distinct subclasses of excitatory neurons in the amygdala. Our cell birth-dating studies reveal that these two populations are born at different times during early neurogenesis, with the amygdala population born before the MSNs. In the striatum, Emx1-lineage neurons represent a unique subpopulation of MSNs: they are disproportionately localized to the dorsal striatum, are found in dopamine receiving, reelin-positive patches, and are born throughout striatal neurogenesis. In addition, our data suggest that a subpopulation of these Emx1-lineage cells originate in the pallium and subsequently migrate to the developing striatum and amygdala. Our intersectional fate-mapping analysis further reveals that Emx1-lineage cells that coexpress Dlx exclusively generate MSNs but do not contribute to the excitatory neurons in the amygdala. Thus, both the timing of neurogenesis and differential combinatorial gene expression appear to be key determinants of striatal versus amygdala fate decisions of Emx1-lineage cells.