MOLECULAR AND ANATOMICAL ANALYSES OF DEVELOPING CORTEX

在哺乳动物中，定位于成年大脑皮层的神经元是由 只有在两个短暂的神经元群体诞生之后。 这些群体被称为亚板块和边缘带细胞，并且 它们在化学和形态上分化为许多不同的细胞。 在经历预先编程的细胞死亡之前的类型。下丘脑区神经元发出 早期轴突进入丘脑、中脑和对侧半球 胎儿的生命，支持它们作为先锋神经元的想法。他们 也是第一批获得功能性的皮质细胞类型 丘脑-皮质突触。大多数子板细胞最终都会死亡，但只有 在皮质-皮质和丘脑-皮质的成人模式之后 连接会建立起来。加在一起，这些和其他观察结果 提示亚板下神经元在脑内具有多种重要功能。 建立大脑皮层回路。如果知道什么的话，那就是很少 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 已经被用来生产一种新的单抗，它可以对神经元进行染色 皮质亚板(Naegele et.这种新抗体选择性地 当该区域的神经元正在经历 预先编程的细胞死亡。拟议的试点研究的目标是 进一步鉴定这种新的单抗抗体，称为亚板-1，并且 表达这种抗原的细胞。在这些先导性研究中，亚盘-1将 与~3H-胸腺嘧啶核苷出生测定放射自显影联合使用 确定亚板最早产生的神经元是否为 弄脏了。染色细胞的形态和神经递质表型 神经元将通过结合使用亚板-1和 细胞内染色和双标记免疫细胞化学。最后， 将使用生化方法来表征抗原本身。 这些研究需要新生的猫和雪貂，主要是因为 几乎所有以前关于亚板细胞发生的时间，形态， 对这些物种的连接性和神经化学进行了研究。 然而，初步结果表明，单抗亚板-1也染色胎儿 猴子和人类亚板，所以任何新的发现都可能是 与人类大脑皮层的发育有关。最终这就是 这些信息可能会进一步加深我们对亚板块在 大脑皮质发育正常，该脑区存在先天缺陷。

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.