Graduate Program in Neuroscience, Vanderbilt University Medical Center, Nashville, TN 37203, USA.
Cereb Cortex. 2011 Jul;21(7):1613-26. doi: 10.1093/cercor/bhq223. Epub 2010 Dec 1.
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.
间质上皮转化因子受体酪氨酸激酶信号调节轴突的生长和发育,并可能有助于调节啮齿动物前脑皮质和边缘回路的连接。但是否存在与自闭症中社会和交流表型相关的变体 MET 等位基因,尚不清楚,但这在很大程度上引起了人们的兴趣。为了开始解决这个问题,我们比较了发育中的小鼠和恒河猴前脑的 Met/MET 蛋白表达。在快速轴突发育和强大的突触形成开始时,表达具有很强的时间保守性。在种间,Met/MET 的表达模式在与边缘相关的结构中几乎完全相同。相比之下,在新皮层中存在高度差异的表达。在小鼠中,Met 广泛分布于整个新皮层。在猕猴中,MET 的表达主要局限于后扣带回、下颞叶、后顶叶和视觉皮层,包括面部处理区域。这种模式与视觉在灵长类动物社会行为中的重要性一致。总的来说,这些数据表明 MET 受体在连接边缘和新皮层回路方面具有保守的发育功能,有助于物种适当的反应,包括社会行为。