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The roles of non-coding and protein-coding genes in the evolutionary expansion of the cerebral cortex

非编码和蛋白质编码基因在大脑皮层进化扩展中的作用

基本信息

批准号：
BB/F003285/1
负责人：
Zoltan Molnar
金额：
$ 68.88万
依托单位：
University of Oxford
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FF003285%2F1
关键词：
roles non coding protein genes

项目摘要

The diversity of brain organizations is spectacular amongst vertebrates. The greatest variations are observed in the dorsal cortex and near its junction to other structures (at the pallial/subpallial boundary). Dorsal cortex of avian and reptilian brains contains only a component of the six layered isocortex of mammals. Although fundamental structures of the isocortex are similar in all mammals, there is a drastic increase in cortical size and complexity in mammals culminating with the human brain. Comparative developmental studies suggest that the elaboration of the mitotic compartments might have been the drive behind mammalian cortical evolution (Rakic, 1995; 2006; Kriegstein et al., 2006; Molnar et al., 2006a,b). The mechanisms and genes responsible for generating these variations can be understood by studying cortical development in various different species. This proposal examines two groups of genes. (1) The first group consists of protein coding genes which are known to be involved in cortical neurogenesis, formation of layers, radial and tangential migration of neurons. (2) The second assortment includes non-coding so-called 'macro-RNA' genes that exhibit distinct signatures of purifying selection, suggestive of functionality. Using the tools of modern genetics and comparative genomics we shall sequence and compare selected groups of genes from both categories and test their function in knockout mice and in in vitro and in vivo experimental paradigms. Through the study of these coding and non-coding genes, we wish to determine, in various taxa, the context in which the most common cortical development genes operate. Comparative aspects of cortical development not only point to evolutionarily relevant changes, but they also draw our attention to the limitations of some of the model systems currently used to understand human cortical developmental abnormalities and indeed reveal the mechanisms responsible for these abnormalities.

在脊椎动物中，大脑组织的多样性是惊人的。最大的变化是在背侧皮质和其交界处附近的其他结构（在苍白球/苍白球下边界）。鸟类和爬行动物大脑的背侧皮层只含有哺乳动物六层同皮质的一部分。虽然同皮质的基本结构在所有哺乳动物中是相似的，但哺乳动物的皮质尺寸和复杂性急剧增加，最终达到人类大脑的高度。比较发育研究表明，有丝分裂区室的精细化可能是哺乳动物皮质进化背后的驱动力（Rakic，1995; 2006; Kriegstein等人，2006; Molnar等人，2006 a，B）。产生这些变异的机制和基因可以通过研究不同物种的皮层发育来理解。这项提议研究了两组基因。(1)第一组由蛋白质编码基因组成，已知其参与皮质神经发生、层的形成、神经元的径向和切向迁移。(2)第二种分类包括非编码的所谓的“宏RNA”基因，它们表现出独特的纯化选择特征，暗示了功能。使用现代遗传学和比较基因组学的工具，我们将测序和比较从两个类别中选择的基因组，并在敲除小鼠和体外及体内实验范例中测试它们的功能。通过这些编码和非编码基因的研究，我们希望确定，在不同的类群，在其中最常见的皮质发育基因的运作。皮质发育的比较方面不仅指向进化相关的变化，但他们也提请我们注意目前用于了解人类皮质发育异常的模型系统的局限性，并确实揭示了这些异常的机制。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Variations of telencephalic development that paved the way for neocortical evolution.

DOI：
10.1016/j.pneurobio.2020.101865
发表时间：
2020-11
期刊：
Progress in neurobiology
影响因子：
6.7
作者：
García-Moreno F;Molnár Z
通讯作者：
Molnár Z

Absence of Tangentially Migrating Glutamatergic Neurons in the Developing Avian Brain.

DOI：
10.1016/j.celrep.2017.12.032
发表时间：
2018-01-02
期刊：
Cell reports
影响因子：
8.8
作者：
García-Moreno F;Anderton E;Jankowska M;Begbie J;Encinas JM;Irimia M;Molnár Z
通讯作者：
Molnár Z

Long noncoding RNA genes: conservation of sequence and brain expression among diverse amniotes.

DOI：
10.1186/gb-2010-11-7-r72
发表时间：
2010
期刊：
Genome biology
影响因子：
12.3
作者：
Chodroff RA;Goodstadt L;Sirey TM;Oliver PL;Davies KE;Green ED;Molnár Z;Ponting CP
通讯作者：
Ponting CP

In search of common developmental and evolutionary origin of the claustrum and subplate