ABSTRACT: The insular cortex has been linked to a multitude of functions. In contrast, the nearby claustrum is a densely connected subcortical region with unclear function. To view the insula-claustrum region from the molecular perspective we analyzed the transcriptomic profile of these areas in six adult and four fetal human brains. We identified marker genes with specific expression and performed transcriptome-wide tests for enrichment of biological processes, molecular functions, and cellular components. In addition, specific insular and claustral expression of genes pertaining to diseases, addiction, and depression was tested. At the anatomical level, we used brain-wide analyses to determine the specificity of our results and to determine the transcriptomic similarity of the insula-claustrum region. We found UCMA to be the most significantly enriched gene in the insular cortex and confirmed specific expression of NR4A2, NTNG2, and LXN in the claustrum. Furthermore, the insula was found to have enriched expression of genes associated with mood disorders, learning, cardiac muscle contraction, oxygen transport, glutamate and dopamine signaling. Specific expression in the claustrum was enriched for genes pertaining to human immunodeficiency virus (HIV), severe intellectual disability, epileptic encephalopathy, intracellular transport, spine development, and macroautophagy. We tested for enrichment of genes related to addiction and depression, but they were generally not highly specific to the insula-claustrum region. Exceptions include high insular expression of genes linked to cocaine abuse and genes associated with ever smoking in the claustrum. Brain-wide, we find that markers of the adult claustrum are most specifically expressed in the fetal and adult insula. Altogether, our results provide a novel molecular perspective on the unique properties of the insula and claustrum.
