Identification and expression profile of novel STAND gene Nwd2 in the mouse central nervous system

In the central nervous system (CNS), neurons need synaptic neurotransmitter release and cellular response for various cellular stress or environmental stimuli. To achieve these highly orchestrated cellular processes, neurons should drive the molecular mechanisms that govern and integrate complex signaling pathways. The signal transduction ATPases with numerous domains (STAND) family of proteins has been shown to play essential roles in diverse signal transduction mechanisms, including apoptosis and innate immunity. However, a comprehensive understanding of STAND genes remains lacking. Previously, we identified the NACHT and WD repeat domain-containing protein 1 (NWD1), a member of STAND family, in the regulation of the assembly of a giant multi-enzyme complex that enables efficient de novo purine biosynthesis during brain development. Here we identified the mouse Nwd2 gene, which is a paralog of Nwd1. A molecular phylogenetic analysis suggested that Nwd1 emerged during the early evolution of the animal kingdom, and that Nwd2 diverged in the process of Nwd1 duplication. RT-PCR and in situ hybridization analyses revealed the unique expression profile of Nwd2 in the developing and adult CNS. Unlike Nwd1, Nwd2 expression was primarily confined to neurons in the medial habenular nucleus, an essential modulating center for diverse psychological states, such as fear, anxiety, and drug addiction. In the adult brain, Nwd2 expression, albeit at a lower level, was also observed in some neuronal populations in the piriform cortex, hippocampus, and substantia nigra pars compacta. NWD2 might play a unique role in the signal transduction required for specific neuronal circuits, especially for cholinergic neurons in the habenula.