Ferri R T, Levitt P
Department of Anatomy and Neurobiology, Medical College of Pennsylvania, Philadelphia 19129, USA.
Development. 1995 Apr;121(4):1151-60. doi: 10.1242/dev.121.4.1151.
Both lineage-based and epigenetic regulation have been postulated as mechanisms to control the formation of discrete areas in the cerebral cortex, but specific genes or signaling pathways that may be involved have yet to be defined. In this paper, we examine whether progenitors, isolated from the cerebral wall prior to neurogenesis, can respond to exogenous cues by adopting a region-specific phenotype. The expression of the limbic system-associated membrane protein (LAMP), a neuron-specific marker of limbic cortical areas, was monitored in cultured neurons arising from precursors harvested from presumptive perirhinal (limbic) and sensorimotor (nonlimbic) zones at embryonic day 12 in the rat. Neuronal phenotype in all cultures was identified by expression of microtubule-associated protein-2 (MAP2). On a substrate of poly-lysine, over 80% of the precursors from the limbic area that differentiate into neurons express a LAMP+ phenotype. Approximately 20% of the neurons generated from precursors of the sensorimotor region become LAMP+. However, modification of the microenvironment had a significant effect on the differentiation of the sensorimotor precursors. When the nonlimbic precursors are grown on Matrigel, there is a 2-fold increase in the number of MAP2+/LAMP+ double-labeled neurons. Dissection of the Matrigel components reveals that in combination with growth factor-deficient Matrigel or collagen type IV, epidermal growth factor and transforming growth factor-alpha increase LAMP expression in the sensorimotor population. Delaying the addition of growth factor until after most cell division had ceased failed to increase the number of LAMP+ neurons. Another growth factor in Matrigel, platelet-derived growth factor, does not produce the same effect. Our results indicate that local signals can regulate the differentiation of cortical progenitors, providing a potential mechanism for establishing an early commitment to specific regional phenotypes in the developing cerebral wall that relate to future functional domains in the cortex.
基于谱系和表观遗传调控都被假定为控制大脑皮层离散区域形成的机制，但可能涉及的特定基因或信号通路尚未明确。在本文中，我们研究了在神经发生之前从脑壁分离的祖细胞是否能通过采用区域特异性表型对外源信号作出反应。在大鼠胚胎第12天从假定的梨状周围（边缘）和感觉运动（非边缘）区域收获的前体细胞产生的培养神经元中，监测边缘系统相关膜蛋白（LAMP）的表达，LAMP是边缘皮质区域的神经元特异性标志物。所有培养物中的神经元表型通过微管相关蛋白2（MAP2）的表达来鉴定。在聚赖氨酸底物上，超过80%分化为神经元的边缘区域前体细胞表达LAMP+表型。约20%由感觉运动区域前体细胞产生的神经元变为LAMP+。然而，微环境的改变对感觉运动前体细胞的分化有显著影响。当非边缘前体细胞在基质胶上生长时，MAP2+/LAMP+双标记神经元的数量增加了两倍。对基质胶成分的剖析表明，与生长因子缺陷型基质胶或IV型胶原结合时，表皮生长因子和转化生长因子-α可增加感觉运动群体中LAMP的表达。将生长因子的添加延迟到大多数细胞分裂停止后并不能增加LAMP+神经元的数量。基质胶中的另一种生长因子血小板衍生生长因子不会产生同样的效果。我们的结果表明，局部信号可以调节皮质祖细胞的分化，为在发育中的脑壁中建立对与皮质未来功能域相关的特定区域表型的早期定向提供了一种潜在机制。
