Development of the Cerebral Cortex in Mammals

哺乳动物大脑皮层的发育

基本信息

批准号：
8488488
负责人：
NADA R ZECEVIC
金额：
$ 33.08万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-05-15 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8488488
关键词：
Address Animal Model Antigens Autistic Disorder Automobile Driving Binding Proteins Brain Brain Diseases Cells Cellular Morphology Cerebral cortex Characteristics Collection Development Developmental Process Dorsal Fresh Tissue Generations Globus Pallidus Goals Green Fluorescent Proteins Histology Human Human Development Immunohistochemistry In Situ Hybridization In Vitro Infection Interneurons Knowledge Lipid Binding Mammals Mental disorders Methods Molecular Mus Neurodevelopmental Disorder Neuroglia Neurons Parvalbumins Pathogenesis Phase Phenotype Population Positioning Attribute Pregnancy Prevention Preventive Intervention Proliferation Marker Pyramidal Cells Radial Reporting Rodent Schizophrenia Somatostatin Source Staging Stem cells Testing Therapeutic Intervention Tissues Transfection Ventricular calbindin calretinin cell type fetal gain of function genetic manipulation improved neocortical nerve stem cell nervous system disorder neurogenesis neuropeptide Y polypeptide progenitor research study spatiotemporal species difference subventricular zone transcription factor

项目摘要

DESCRIPTION (provided by applicant): The long-term objective of this proposal is to improve our understanding of development of the human cerebral cortex, and cortical interneurons in particular. Cortical interneurons are necessary for building and fine-tuning of the cortical microcircuitry as they provide inhibitory input to principal (pyramidal) cells. In rodents, the majority of cortical interneurons is derived from the ventral pallidum (ganglionic eminences, GE). They subsequently migrate tangentially into the dorsal cerebral cortex. In the human brain, however, several reports have shown that cortical interneurons may originate both in the GE and in the neocortical ventricular/subventricular zones. The much longer developmental period, size, complexity of the human cerebral cortex and various subtypes of interneurons implicate inter-species differences. Thus, information derived from animal models, although very useful, can not be directly applied to humans. However, to be able to cure various psychiatric and neurological disorders, we need to better understand human brain. Three Specific Aims will be addressed: 1. Cortical interneuron's progenitors in the human fetal brain. 2. Ventral transcription factors in the human fetal brain, and 3. Do radial glia and/or intermediate progenitors contribute to human cortical interneuron population? Methods of classical histology, immunohistochemistry, in situ hybridization, and in vitro genetic manipulation methods will be used. We will relate some of the findings in the human fetal brain to the developing mouse brain so that issues relevant to species-dependent differences can be addressed. A key premise is that a diversity of cortical progenitor cells is necessary to achieve the complexity of the human cerebral cortex. The experimental approaches proposed here are not typically used to study the human fetal brain, but we expect they will yield important information about basic mechanisms regulating the initial cortical organization in humans. The knowledge about human cortical interneurons is fundamental for understanding normal developmental processes, as well as congenital and psychiatric brain disorders, such as schizophrenia or autism, and may contribute to their prevention and treatment. Having available to us a well- characterized collection of human fetal brains, an opportunity to obtain fresh tissue, and expertise in this field, we are in a favorable position to perform proposed experiments.

描述（由申请人提供）：该提案的长期目标是提高我们对人类脑皮质的发展的理解，尤其是皮质中间神经元。皮质中间神经元对于对皮质微环流的建造和微调是必要的，因为它们为主（金字塔）细胞提供了抑制性输入。在啮齿动物中，大多数皮质中间神经元源自腹侧胶囊（神经节象征，GE）。随后，它们切向迁移到背脑皮质中。然而，在人脑中，有几份报告表明，皮质中间神经元可能起源于GE和新皮层室/室内区域。更长的发育周期，大小，人脑皮质的复杂性和中间神经元的各种亚型都暗示了种间差异。因此，源自动物模型的信息虽然非常有用，但不能直接应用于人类。但是，要能够治愈各种精神病和神经系统疾病，我们需要更好地了解人脑。将解决三个具体目标：1。皮质间神经元在人胎儿大脑中的祖细胞。 2。人胎儿脑中的腹侧转录因子，3。径向胶质细胞和/或中间祖细胞是否有助于人类皮质间核元种群？将使用经典组织学，免疫组织化学，原位杂交和体外遗传操纵方法的方法。我们将将人类胎儿大脑中的一些发现与发育中的小鼠大脑联系起来，以便可以解决与物种依赖性差异有关的问题。一个关键的前提是，需要多种皮质祖细胞来实现人脑皮质的复杂性。这里提出的实验方法通常不用于研究人类胎儿大脑，但我们希望它们将产生有关调节人类最初皮质组织的基本机制的重要信息。关于人皮质中间神经元的知识对于理解正常发育过程以及先天性和精神病脑疾病（例如精神分裂症或自闭症）至关重要，并且可能有助于他们的预防和治疗。在我们可以使用人类胎儿大脑的特征收集，获得新鲜组织的机会以及在该领域的专业知识的机会，我们处于执行提出的实验的有利位置。

项目成果

期刊论文数量（23）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

COUP-TFII expressing interneurons in human fetal forebrain.

DOI：
10.1093/cercor/bhr359
发表时间：
2012-12
期刊：
Cerebral cortex
影响因子：
3.7
作者：
G. Reinchisi;K. Ijichi;N. Glidden;I. Jakovcevski;N. Zečević
通讯作者：
G. Reinchisi;K. Ijichi;N. Glidden;I. Jakovcevski;N. Zečević

Spontaneous electrical activity in the human fetal cortex in vitro.

DOI：
10.1523/jneurosci.3886-10.2011
发表时间：
2011-02-16
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Moore AR;Zhou WL;Jakovcevski I;Zecevic N;Antic SD
通讯作者：
Antic SD

Neurogenesis continues in the third trimester of pregnancy and is suppressed by premature birth.

DOI：
10.1523/jneurosci.4445-12.2013
发表时间：
2013-01-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Malik S;Vinukonda G;Vose LR;Diamond D;Bhimavarapu BB;Hu F;Zia MT;Hevner R;Zecevic N;Ballabh P
通讯作者：
Ballabh P

The Role of Sonic Hedgehog in the Specification of Human Cortical Progenitors In Vitro.