MOLECULAR AND ANATOMICAL ANALYSES OF DEVELOPING CORTEX

在哺乳动物中， 只有在两个短暂的神经元群体出生之后。 这些细胞群被称为亚板细胞和边缘区细胞， 它们分化成许多化学和形态上不同细胞 在经历前程序性细胞死亡之前的类型。亚板神经元发送 轴突进入丘脑，中脑和对侧半球早在 支持了它们作为先驱神经元的观点。他们 也是第一种接受功能性 丘脑-皮层突触大多数亚板细胞最终死亡，但只有 在成人皮质-皮质和丘脑-皮质模式之后， 连接已经建立。总之，这些和其他观察 这表明亚板神经元在神经系统中具有许多重要功能， 建立皮层回路如果说有什么是已知的， 这些功能背后的分子机制。 一种寻找亚板特异性分子的免疫学方法， 已经被用来生产一种新的单克隆抗体， 皮质亚板（Naegele et. al. '89）。这种新抗体选择性地 当这个区域的神经元经历 程序性细胞死亡拟议试点研究的目标是 进一步表征这种新的mAb抗体，称为Subplate-1， 表达这种抗原的细胞。在这些初步研究中，将使用Subplate-1 与3 H-胸苷出生日期放射自显影术联合使用， 确定基板的最早产生的神经元是否 弄脏了染色的细胞形态和神经递质表型 将通过使用Subplate-1结合 细胞内染色和双标记免疫细胞化学。最后， 将使用生物化学方法来表征抗原本身。 这些研究将需要新生猫和雪貂，主要是因为 几乎所有以前关于亚板细胞发生，形态， 连接和神经化学已经在这些物种中进行了研究。 然而，初步结果表明，mAb Subplate-1也染色胎儿， 猴子和人类的亚板，所以很可能任何新的发现都可以 与人类大脑皮层的发育有关。最终这 这些信息可以进一步了解亚板块在 正常的皮质发育和这一大脑区域的先天性缺陷。

In mammals, neurons destined for the adult cerebral cortex are generated only after the period when two transient neuronal populations are born. These populations are called the subplate and the marginal zone cells, and they differentiate into many chemically and morphologically distinct cell types before undergoing preprogrammed cell death. Subplate neurons send axons into the thalamus, midbrain and contralateral hemisphere early in fetal life, supporting the idea that they function as pioneer neurons. They are also the first cortical cell types to receive functional thalamo-cortical synapses. Most subplate cells eventually die, but only after the adult pattern of cortico-cortical and thalamo-cortical connections become established. Together, these and other observations indicate that subplate neurons have a number of important functions in establishing cortical circuits. Little, if anything is known about molecular mechanisms underlying these functions. An immunological approach to search for subplate specific molecules has been used to produce a new monoclonal antibody which stains neurons in the cortical subplate (Naegele et. al.'89). This new antibody selectively stains the cortical subplate when neurons in this region are undergoing preprogrammed cell death. The goal of the proposed pilot studies is to further characterize this new mAb antibody, called Subplate-1, and the cells that express this antigen. In these pilot studies,Subplate-1 will be used in combination with 3H-thymidine birth-dating autoradiography to determine whether the earliest generated neurons of the subplate are stained. The morphology and neurotransmitter phenotypes of the stained neurons will be determined by using Subplate-1 in combination with intracellular staining and double-label immunocytochemistry. Finally, biochemical approaches will be used to characterize the antigen itself. These studies will require neonatal cats and ferrets principally because nearly all previous work on the times of subplate cell genesis, morphology, connectivity and neurochemistry have been studied in these species. However, preliminary results indicate that mAb Subplate-1 also stains fetal monkey and human subplate, so it is likely that any new findings can be related to the development of the human cerebral cortex. Eventually this information may further our understanding of the role of the subplate in normal cortical development and in congenital defects of this brain region.