Nurr1 Orchestrates Claustrum Development and Functionality

Claustrum is the part of the forebrain known to be most widely interconnected tissue with almost all brain 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, cell fate specification, connectivity and thus behaviors. Nurr1-deficient claustral cells aberrantly migrate into insular cortex, shaping claustrum from a crescent-like into a wing-like structure. These cells ectopically turn on insular cortex genetic programs that were verified by single cell transcriptomics. Accordingly, functional connectivity of the claustrum is not properly formed and relevant behaviors are dysregulated in Nurr1-deficient mice. Additionally, we show that Nurr1 regulates claustral neuron positioning and cell fate by suppressing Gαs-PKA signaling.