Selective neuronal expression of the SoxE factor, Sox8, in direct pathway striatal projection neurons of the...

The striatum is the major component of the basal ganglia and is well known to play a key role in the control of motor function via balanced output from the indirect (iSPNs) and direct pathway striatal projection neurons (dSPNs). Little is known, however, about the molecular genetic mechanisms that control the formation of the iSPNs versus dSPNs. We show here that the SoxE family member, Sox8, is co-expressed with the dSPN markers, Isl1 and Ebf1, in the developing striatum. Moreover, dSPNs, as marked by Isl1-cre fate map, express Sox8 in the embryonic striatum and Sox8-EGFP BAC transgenic mice specifically reveal the direct pathway axons during development. These EGFP⁺ axons are first observed to reach their midbrain target, the substantia nigra pars reticulata (SNr), at E14 in the mouse with a robust connection observed already at birth. The selective expression of EGFP in dSPNs of Sox8-EGFP BAC mice is maintained at postnatal timepoints. Sox8 is known to be expressed in oligodendrocyte precursor cells (OPCs) together with other SoxE factors and we show here that the EGFP signal co-localizes with the OPC markers throughout the brain. Finally, we show that Sox8-EGFP BAC mice can be used to interrogate the altered dSPN development in Isl1 conditional mutants including aberrant axonal projections detected already at embryonic timepoints. Thus, Sox8 represents an early and specific marker of embryonic dSPNs and the Sox8-EGFP BAC transgenic mice are an excellent tool to study the development of basal ganglia circuitry.