Satb1 Is an Activity-Modulated Transcription Factor Required for the Terminal Differentiation and Connectivity of Medial Ganglionic Eminence-Derived Cortical Interneurons

• DOI: 10.1523/jneurosci.3583-12.2012
• Publication Date: 2012-12-05T17:46:54Z
• Authors: Jennie Close; Han Xu; Natalia De Marco ...; Renata Batista-Brito; Elsa Rossignol; Bernardo Rudy; Gord Fishell
• Keywords: Cerebral Cortex; 0303 health sciences; Cell Survival; Presynaptic Terminals; Excitatory Postsynaptic Potentials; Gene Expression Regulation, Developmental; Cell Differentiation; Mice, Transgenic; Neural Inhibition; Matrix Attachment Region Binding Proteins; Brain Waves; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Parvalbumins; Cell Movement; Interneurons; Animals; Somatostatin; Transcription Factors

Although previous work identified transcription factors crucial for the specification and migration of parvalbumin (PV)-expressing and somatostatin (SST)-expressing interneurons, the intrinsic factors required for the terminal differentiation, connectivity, and survival of these cell types remain uncharacterized. Here we demonstrate that, within subpopulations of cortical interneurons,Satb1(special AT-rich binding protein) promotes terminal differentiation, connectivity, and survival in interneurons that express PV and SST. We find that conditional removal ofSatb1in mouse interneurons results in the loss of a majority of SST-expressing cells across all cortical layers, as well as some PV-expressing cells in layers IV and VI, by postnatal day 21. SST-expressing cells initially migrate to the cortex inSatb1mutant mice, but receive reduced levels of afferent input and begin to die during the first postnatal week. Electrophysiological characterization indicates that loss ofSatb1function in interneurons results in a loss of functional inhibition of excitatory principal cells. These data suggest that Satb1 is required for medial ganglionic eminence-derived interneuron differentiation, connectivity, and survival.