Transcriptomic insights into subtype specification and compartmentalization of striatal spiny projection neurons

However, the cell basis underlying subtype specification especially that of eSPNs, and mechanisms governing the complementary patterning remain unclear. Here, employing sc-RNA sequencing combined with loss-of-function we find that deletion of the transcription factor Foxg1 forces both dSPNs and iSPNs into an eSPN fate in vLGE lineage and drives dLGE/CGE to adopt a vLGE identity.

We profile the developmental trajectories and reveal FOXG1-driven transcriptional programs that specify the four subtypes. We identify key TFs controlling specification of each SPN subtype. Further, we find that postmitotic Foxg1 deletion impairs the formation of striatal complementary patch and matrix and uncover that FOXG1-driven cell migration and cell adhesion-related molecules to control striatal compartmentalization.