Selective Lis1 inactivation disrupts migration and positioning of cortical somatostatin interneurons.

One subtype of interneurons, classified by their neurochemical properties, are somatostatin-positive (SST+) interneurons, which express somatostatin along with GABA and form synapses with both pyramidal neurons and other interneurons. SST+ interneurons originate in the medial ganglionic eminence and migrate tangentially to the cortex, making them potentially vulnerable to gene mutations linked to neuronal migration disorders. The Lis1 gene (Pafah1b1) regulates dynein-mediated motility, mitosis, and microtubule organization. Mutations in Lis1 are associated with lissencephaly and cortical disorganization. To investigate its role, we developed a mouse model with Lis1 deletion specifically in SST+ interneurons. We studied the anatomical and developmental effects of this deletion, focusing on tangential migration during embryonic and early postnatal stages. We analyzed SST+ interneuron numbers in the cingulate cortex (anterior and retrosplenial regions) of young mutant mice (P30). Our findings show a reduction in SST+ interneurons in mutants compared to controls, indicating impaired migration and/or maturation. Further research is needed to uncover the mechanisms behind this reduction and to determine its functional implications.