Nurr1 orchestrates claustrum development and functionality

Claustrum is the part of the forebrain known to be most widely interconnected tissue with almost all global regions. It is believed to be involved in coordinating multiple cognitive behaviors including consciousness formation. However, little is known about the molecular mechanisms underlying its development and involvement in behavioral control. Here we show that Nurr1 (Nr4a2) is the key transcription factor orchestrating claustral morphogenesis, functional connectivity and thus behaviors. Nurr1 deficient claustral cells aberrantly migrate into insular cortex, shaping claustrum into an abnormal wing-like structure, and ectopically turn on insular cortex genetic program. Accordingly, functional connectivity of the claustrum is not properly formed and relevant behaviors are dysregulated in Nurr1 deficient mice. We show that Nurr1 regulates claustral neuron positioning by suppressing G-protein signaling. P0 anterior claustro-insular parts of mouse cerebral cortices (amygdala, hippocampal and posterior cortical tissues were manually excluded) were dissociated. Approximately 10,000 nuclei were prepared for single-nuclei encapsulation using a 10X single cell controller for each genotype.10x Genomics 3' v3 gene expression (GEX) libraries were prepared and sequenced on a single Novaseq sequencing system. Sex was not discriminated in this project or single cell transcriptomic analysis.