Conserved Subcortical and Divergent Cortical Expression of Proteins Encoded by Orthologs of the Autism Risk Gene MET

Met receptor tyrosine kinase signaling regulates the growth and development of axons and may contribute to the wiring of cortical and limbic circuits in the rodent forebrain. Whether the orthologous MET receptor functions similarly in the developing primate forebrain is not known but is of considerable interest considering the association of variant MET alleles with social and communication phenotypes in autism. To begin addressing this question, we compared Met/MET protein expression in the developing mouse and rhesus macaque forebrain. There was a strong temporal conservation of expression during the time of rapid axon development and the onset of robust synapse formation. Expression patterns of Met/MET in limbic-related structures were almost identical between species. In marked contrast, there was highly divergent expression in the neocortex. In mouse, Met was broadly distributed throughout neocortex. In the macaque, robust MET expression was largely restricted to the posterior cingulate, inferior temporal, posterior parietal, and visual cortices, including face processing regions. The pattern is consistent with the importance of vision in the social repertoire of the primate. Collectively, these data suggest a conserved developmental function of the MET receptor in wiring together limbic and neocortical circuits that facilitate species-appropriate responses, including social behavior.