Cajal-Retzius Cells in Developing Cerebral Cortex

大脑皮层发育中的 Cajal-Retzius 细胞

• 批准号: 6639757
• 负责人: NADA R ZECEVIC
• 金额: $ 29.32万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-15 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6639757
• 关键词: DNA binding protein; GABA receptor; cell population study; cerebral cortex; developmental neurobiology; electron microscopy; embryo /fetus cell /tissue; gene expression; glutamate receptor; human tissue; immunocytochemistry; in situ hybridization; laboratory mouse; mammalian embryology; morphometry; nervous system disorder diagnosis; neuroanatomy; neurogenesis; neurons; polymerase chain reaction; protein localization; protein structure function; species difference; statistics /biometry; voltage /patch clamp

The long-term objective of this proposal is to contribute to the understanding of the initial development of the cerebral cortex. Specifically, we propose to study the role of human Cajal-Retzius (C-R) cells and layer I during early development. The overriding hypothesis to be tested is that the C-R cells are a diverse population of cells and that species- related differences in this diversity accounts for the fate of these cells during development. Cajal-Retzius cells are the main type of cell in the initial layer I (the preplate). By secreting the glycoprotein, reelin, C-R cells have been postulated to control the inside-out migration of cortical neurons and thus to play a fundamental morphogenic role in corticogenesis. The disruption of this process has been implicated in various neurodevelopmental disorders resulting in mental retardation, ectopias and epilepsy. In order to understand and ultimately prevent these pediatric disorders, there is a need to gain an appreciation of the mechanisms underlying normal brain development. Recent studies employing new markers of early cortical neurons reveal a cellular composition of the human preplate that is much more complex than the prevailing classical model. In this application, we propose 3 specific aims to address some of the most controversial and pressing issues related to C-R cells in human cortical development. We would like to know the answers to the following questions: (1) Do all C-R cells belong to a single unique class of cells or should they be classified instead into different subtypes on the basis of their antigenic phenotype, survival rate and transmitter receptor properties? (2) Are C-R cells generated at different times and from different places? (3) How do species- specific differences relate to functional properties, the survival and possible new roles of C-R cells in humans? Having available to us a well-characterized collection of human brains that spans the intrauterine period of development, we are in a uniquely favorable position to answer these questions. Normal development of the cerebral cortex is essential for proper functioning of the adult central nervous system. Data generated through this research will advance our understanding of normal brain development, and point to possible mechanisms that contribute to congenital brain malformations. In addition, our findings will establish a prerequisite set of baseline data for proper diagnosis and treatment of pediatric disorders of the CNS.

该提案的长期目标是为理解大脑皮层的初始发展做出贡献。 具体而言，我们建议研究人类Cajal-Retzius（C-R）细胞和I层在早期发育过程中的作用。 要测试的压倒性假设是，C-R细胞是各种细胞群，并且这种多样性的物种与物种相关的差异构成了这些细胞在发育过程中的命运。 Cajal-Retzius细胞是初始层I（预序）中的主要类型。 通过分泌糖蛋白，reelin，已经假定C-R细胞来控制皮质神经元的内而外迁移，从而在皮质生成中起基本的形态学作用。 该过程的破坏与各种神经发育障碍有关，导致智力低下，骨膜和癫痫。为了理解并最终预防这些小儿疾病，需要对正常脑发育的基础机制表示赞赏。 最近采用早期皮质神经元标记物的研究表明，人类预序的细胞组成比流行的经典模型要复杂得多。 在本应用程序中，我们提出了3个具体旨在解决与人类皮质发育中与C-R细胞有关的最具争议和紧迫的问题。 我们想知道以下问题的答案：（1）所有C-R细胞是否属于单个独特的单元格，还是应该根据其抗原表型，生存率和发射机受体特性将它们分类为不同的亚型？ （2）C-R细胞是否在不同的时间和不同地方产生？ （3）物种特异性差异与功能特性，C-R细胞在人类中的生存和可能的新作用有何关系？ 我们可以使用涵盖宫内发育时期的人类大脑的特征性收集，我们处于一个独特的好处来回答这些问题。大脑皮层的正常发育对于成人中枢神经系统的正常功能至关重要。 通过这项研究产生的数据将提高我们对正常脑发育的理解，并指出导致先天性脑畸形的可能机制。 此外，我们的发现将建立一组先决条件的基线数据，以适当诊断和治疗中枢神经系统的小儿疾病。