Goldshmit Yona, Homman-Ludiye Jihane, Bourne James A
Australian Regenerative Medicine Institute, Monash University, Building 75, Clayton, Vic., 3800, Australia.
Eur J Neurosci. 2014 May;39(9):1419-28. doi: 10.1111/ejn.12514. Epub 2014 Mar 11.
Ephs form the largest family of receptor tyrosine kinases. They interact with the membrane-bound ligands - ephrins - to control crucial aspects of brain development. EphA4 is the most prominent member of the family in terms of versatility and ability to bind most ephrin ligands. EphA4 regulates brain development by modulating neuronal migration and connectivity. In the present study, we address the involvement of EphA4 in patterning the primary visual cortex (V1) of the marmoset monkey by characterizing the cellular expression profile of EphA4 from late embryonic stages to adulthood. We identified continuous expression on neurons in the cortical plate and mature neocortical layers, similar to that described in the mouse, excluding a role for EphA4 in the formation of borders between visual areas in the marmoset neocortex. In addition to neurons, we also report expression of EphA4 on glial populations, including radial glia and astrocytes. In contrast to what is seen in the mouse, EphA4 expression on astrocytes persists in the adult marmoset V1, including around blood vessels and in the white matter. Robust expression by glial populations, which retain neurogenic properties in the postnatal marmoset, indicates that EphA4 may have acquired additional roles during evolution, with important implications for the benefits of EphA4-blocking therapies following brain injury.
Eph家族构成了受体酪氨酸激酶中最大的一个家族。它们与膜结合配体——ephrin相互作用,以控制大脑发育的关键方面。就多功能性以及结合大多数ephrin配体的能力而言,EphA4是该家族中最突出的成员。EphA4通过调节神经元迁移和连接来调控大脑发育。在本研究中,我们通过描绘从胚胎后期到成年期EphA4的细胞表达谱,探讨EphA4在狨猴初级视皮层(V1)模式形成中的作用。我们发现在皮质板和成熟新皮层各层的神经元上持续表达EphA4,这与在小鼠中描述的情况类似,排除了EphA4在狨猴新皮层视觉区域边界形成中的作用。除了神经元,我们还报道了EphA4在包括放射状胶质细胞和星形胶质细胞在内的胶质细胞群体上的表达。与在小鼠中看到的情况不同,EphA4在成年狨猴V1星形胶质细胞上的表达持续存在,包括在血管周围和白质中。胶质细胞群体在出生后的狨猴中保留神经源性特性,其EphA4的强烈表达表明EphA4在进化过程中可能获得了额外的作用,这对于脑损伤后EphA4阻断疗法的益处具有重要意义。