# Nurr1 Orchestrates Claustrum Development and Functionality

## TL;DR

This study reveals that Nurr1 is a key transcription factor controlling claustrum development and function, impacting brain connectivity and behavior.

## Contribution

The study identifies Nurr1 as a master regulator of claustrum morphogenesis and cell fate through suppression of Gαs-PKA signaling.

## Key findings

- Nurr1 deficiency causes claustral cells to migrate into the insular cortex, altering its structure.
- Nurr1 suppresses Gαs-PKA signaling to regulate claustral neuron positioning and fate.
- Defective claustrum development in Nurr1-deficient mice leads to impaired connectivity and cognition.

## Abstract

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.

Nurr1 (Nr4a2) is the master transcription factor to control claustrum morphogenesis and cell fate decision postmitotically by inhibiting intracellular G‐protein signaling. Nurr1 deficiency alters the transcriptomic profiles of subcortical claustral neurons into neocortical insular neurons, resulting in defected claustrum development, impaired axonal wiring and functional connectivity, and thus disturbed claustrum dependent cognition.