We describe the role of Sox6 in cortical
interneuron development, from a cellular to a behavioral level. We identify Sox6 as a protein expressed continuously within MGE-derived cortical
interneurons from
postmitotic progenitor stages into adulthood. Both its expression pattern and null
phenotype suggests that Sox6 gene function is closely linked to that of Lhx6. In both Lhx6 and Sox6 null animals, the expression of PV and SST and the position of both
basket and Martinotti
neurons are abnormal. We find that Sox6 functions downstream of Lhx6.
Electrophysiological analysis of Sox6
mutant cortical
interneurons revealed that
basket cells, even when mispositioned, retain characteristic but immature fast-spiking physiological features. Our data suggest that Sox6 is not required for the specification of MGE-derived cortical
interneurons. It is, however, necessary for their normal positioning and maturation. As a consequence, the specific removal of Sox6 from this population results in a severe
epileptic encephalopathy.
