The CHD8/CHD7/Kismet family links blood-brain barrier glia and serotonin to ASD-associated sleep defects
Mireia Coll-Tané, Naihua N. Gong, Samuel J. Belfer, Lara V. van Renssen, Evangeline C. Kurtz‐Nelson, Milán Szuperák, Ilse Eidhof, Boyd van Reijmersdal, Isabel Terwindt, Jaclyn Durkin, Michel M. M. Verheij, Chang N. Kim, Caitlin M. Hudac, Tomasz J. Nowakowski, Raphael Bernier, Sigrid Pillen, Rachel K. Earl, Evan E. Eichler, Tjitske Kleefstra, Matthew S. Kayser, Annette Schenck
Abstract
ortholog. We show that Kismet is required in glia for early developmental and adult sleep architecture. This role localizes to subperineurial glia constituting the blood-brain barrier. We demonstrate that Kismet-related sleep disturbances are caused by high serotonin during development, paralleling a well-established but genetically unsolved autism endophenotype. Despite their developmental origin, Kismet's sleep architecture defects can be reversed in adulthood by a behavioral regime resembling human sleep restriction therapy. Our findings provide fundamental insights into glial regulation of sleep and propose a causal mechanistic link between the CHD8/CHD7/Kismet family, developmental hyperserotonemia, and autism-associated sleep disturbances.