Spatial-temporal expression map of the whole-brain proteome of domestic dogs

With a long history of co-evolution and co-adaptation with humans, dogs have evolved exquisite and complex cross-species social and cognitive abilities. Thus, the domestic dog offers a unique opportunity to understand the development and functioning of the human brain, in particular social and cognitive functions.

A research team led by Professor Zhang Yonging from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences recently conducted a comparative study of postnatal brain development in humans, dogs and mice. The study was published online in Molecular and Cellular Proteomics June 20.

The precise spatial and temporal regulation of protein expression, the executors of biological function, is crucial for brain development and function. Postnatal development is as important as embryonic development. However, only adult human and mouse brains have been systematically analyzed at the proteomic level. The researchers quantitatively profiled the proteomes of six brain regions including the cerebellar cortex, olfactory, hippocampus, prefrontal cortex, amygdala and striatum across three stages of postnatal development: neonatal, juvenile and adult.

Their results demonstrated that different regions of the brain have distinct cytoarchitecture, function, and progression of myelination. Cross-regional expression profiles of orthologous proteins, particularly those involved in mitochondria-related pathways, were similar between dog and human, but different between mouse and human. The similarity in protein expressions is consistent with conserved cis-regulatory element frequency (CREF) modules between dog and human.

“We have been working on autism research for more than 15 years. After getting the data, what we really want to know is the spatial expression pattern of proteins linked to psychiatric diseases among species,” said said Professor Zhang, corresponding author of the study.

Many human psychiatric disorders, in which deficits in social cognition are a core feature, have apparent canine analogues. “We identified 328 protein orthologues associated with autism spectrum disorders and schizophrenia (ASD/Scz) expressed in the brains of all three species and showed that cross-regional expression of ASD/Scz protein in dog brain was significantly more similar to that of humans than in mouse brains,” said Dr. Hong Huilin, first author of the study.

“This study provides important information to guide the mechanistic and translational study of human brain diseases using appropriate animal models,” said Professor Zhang Yaping, Fellow of the Chinese Academy of Sciences.