A transcriptomic atlas of 11 canine brain regions and the pituitary gland

Psychiatric disorders impose a substantial global burden and exhibit marked inter-individual heterogeneity. To better capture this complexity, dogs have been proposed as a complementary translational model for studying brain function and neuropsychiatric traits. However, transcriptomic studies spanning multiple regions of the canine brain remain limited. Here, we performed RNA-seq across 11 brain regions and the pituitary gland from 4 healthy dogs to characterize transcriptional regulation at multiple molecular layers. Unsupervised clustering identified three transcriptional groups among the brain regions, while the pituitary formed a distinct cluster. A similar regional transcriptional grouping was observed in the primate dataset. The cortical–limbic regions (CLR) group showed enrichment in synaptic plasticity and dendrite development, whereas the subcortical regions (SCR) group was associated with sensory perception processes. The olfactory bulb (OB) showed reduced enrichment of neuronal developmental pathways, and the pituitary (Pit) exhibited a distinct pituitary developmental signature. A synaptic plasticity-related transcriptional module featured CAMK2A and GRIN2A as hub genes. Motif-based analysis identified SP4 and BCL11B as candidate regulators of this module, with distinct inferred activities across transcriptional groups. At the post-transcriptional level, alternative splicing showed group-specific patterns, and a subset of differentially spliced regions overlapped dog-specific positive-selection intervals. Permutation analyses did not support significant enrichment above random expectation. Finally, region-specific transcriptional signatures showed significant enrichment for human neuropsychiatric trait heritability. Together, these results provide a multi-region canine brain and pituitary transcriptomic resource for cross-species comparisons of regional molecular signatures.