Maturation-Promoting Activity of SATB1 in MGE-Derived Cortical Interneurons

SummaryThe generation of cortical interneuron subtypes is controlled by genetic programs that are activated in the ventral forebrain and unfold during the prolonged period of inhibitory neuron development. The LIM-homeodomain protein LHX6 is critical for the development of all cortical interneurons originating in the medial ganglionic eminence, but the molecular mechanisms that operate downstream of LHX6 to control the terminal differentiation of somatostatin- and parvalbumin-expressing interneurons within the cortex remain unknown. Here, we provide evidence that the nuclear matrix and genome organizer protein SATB1 is induced by neuronal activity and functions downstream of Lhx6 to control the transition of tangentially migrating immature interneurons into the terminally differentiated Somatostatin (SST)-expressing subtype. Our experiments provide a molecular framework for understanding the genetic and epigenetic mechanisms by which specified but immature cortical interneurons acquire the subtype-defining molecular and morphophysiological characteristics that allow them to integrate and function within cortical circuits.

Graphical AbstractFigure optionsDownload as PowerPoint slideHighlights
► Satb1 is specifically expressed in MGE-derived cortical interneurons
► Satb1 is required for the maturation of MGE-derived cortical interneurons in vivo
► Satb1 promotes the maturation of SST+ cortical interneurons downstream of Lhx6
► Neuronal activity induces expression of Satb1 in immature cortical interneurons