Evolutionary mechanisms of neoteny and enlargement of the human cerebral cortex
人类大脑皮层幼态持续和扩大的进化机制
基本信息
- 批准号:EP/Z000718/1
- 负责人:
- 金额:$ 221.7万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2024
- 资助国家:英国
- 起止时间:2024 至 无数据
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
The human brain is greatly enlarged compared with other mammals and even our closest living relatives, the other great apes. The neocortex is thought to contribute to higher cognitive capabilities, and as such its enlargement is likely a major contributor to our success as a species. However, the evolutionary mechanisms responsible for this enlargement are still unclear. In particular, which of the many human-specific genetic changes are responsible for expansion of the cerebral cortex are unknown. Increasing evidence points to a delay in development, or neoteny, as being important for enabling increased neuron production and size, yet how that delay comes about is also not known. In this proposal, we will use human and nonhuman ape cerebral organoids to examine this question and to uncover which genetic loci and developmental signalling processes have been key to human-specific cortical size determination. We will use a combination of multi-omics approaches to probe the epigenetic and metabolic signatures of cortical progenitors at various stages, to reveal key regulators of neural fate and identify human-specific changes that allow for delayed differentiation and thus protracted progenitor expansion. We will also investigate extrinsic, cerebrospinal fluid derived signals secreted by the choroid plexus, a brain tissue exhibiting key developmental differences in the human fetal brain. Finally, pharmacological and genetic perturbations, including cross-species genetic locus swapping experiments, will functionally test whether the identified regulators and their relevant human-specific genetic changes have a causal role in progenitor and neuron expansion. This combination of state-of-the-art organoid, omics, and genetic engineering approaches will reveal not only which factors regulate timing and cell fate, but also which evolutionary genetic changes are responsible for human brain expansion.
与其他哺乳动物,甚至与我们的近亲——其他类人猿相比,人类的大脑要大得多。新皮层被认为有助于提高认知能力,因此它的扩大可能是我们作为一个物种成功的主要因素。然而,导致这种扩大的进化机制仍不清楚。特别是,在许多人类特有的基因变化中,哪一个是导致大脑皮层扩张的原因尚不清楚。越来越多的证据表明,发育的延迟或幼发性对于增加神经元的产生和大小很重要,但这种延迟是如何产生的还不清楚。在本提案中,我们将使用人类和非人类猿类大脑器官来研究这个问题,并揭示哪些遗传位点和发育信号过程是决定人类特异性皮质大小的关键。我们将结合多组学方法来探索皮层祖细胞在不同阶段的表观遗传和代谢特征,揭示神经命运的关键调节因子,并确定允许延迟分化的人类特异性变化,从而延长祖细胞的扩展。我们还将研究脉络膜丛分泌的外源性脑脊液来源信号,脉络膜丛是人类胎儿大脑中表现出关键发育差异的脑组织。最后,药理学和遗传扰动,包括跨物种遗传位点交换实验,将从功能上测试确定的调节因子及其相关的人类特异性遗传变化是否在祖细胞和神经元扩张中起因果作用。这种最先进的类器官、组学和基因工程方法的结合,不仅将揭示哪些因素调节时间和细胞命运,而且还将揭示哪些进化基因变化是人类大脑扩张的原因。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Madeline Lancaster其他文献
Modelling human brain development and disease with organoids
利用类器官模拟人类大脑发育和疾病
- DOI:
10.1038/s41580-024-00804-1 - 发表时间:
2024-12-12 - 期刊:
- 影响因子:90.200
- 作者:
Marcella Birtele;Madeline Lancaster;Giorgia Quadrato - 通讯作者:
Giorgia Quadrato
Madeline Lancaster的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
相似国自然基金
Exploring the Intrinsic Mechanisms of CEO Turnover and Market
- 批准号:
- 批准年份:2024
- 资助金额:万元
- 项目类别:外国学者研究基金
Exploring the Intrinsic Mechanisms of CEO Turnover and Market Reaction: An Explanation Based on Information Asymmetry
- 批准号:W2433169
- 批准年份:2024
- 资助金额:万元
- 项目类别:外国学者研究基金项目
Erk1/2/CREB/BDNF通路在CSF1R相关性白质脑病致病机制中的作用研究
- 批准号:82371255
- 批准年份:2023
- 资助金额:49.00 万元
- 项目类别:面上项目
Foxc2介导Syap1/Akt信号通路调控破骨/成骨细胞分化促进颞下颌关节骨关节炎的机制研究
- 批准号:82370979
- 批准年份:2023
- 资助金额:48.00 万元
- 项目类别:面上项目
MYRF/SLC7A11调控施万细胞铁死亡在三叉神经痛脱髓鞘病变中的作用和分子机制研究
- 批准号:82370981
- 批准年份:2023
- 资助金额:48.00 万元
- 项目类别:面上项目
Idh3a作为线粒体代谢—表观遗传检查点调控产热脂肪功能的机制研究
- 批准号:82370851
- 批准年份:2023
- 资助金额:48.00 万元
- 项目类别:面上项目
声致离子电流促进小胶质细胞M2极化阻断再生神经瘢痕退变免疫机制
- 批准号:82371973
- 批准年份:2023
- 资助金额:48.00 万元
- 项目类别:面上项目
GREB1突变介导雌激素受体信号通路导致深部浸润型子宫内膜异位症的分子遗传机制研究
- 批准号:82371652
- 批准年份:2023
- 资助金额:45.00 万元
- 项目类别:面上项目
用于小尺寸管道高分辨成像荧光聚合物点的构建、成像机制及应用研究
- 批准号:82372015
- 批准年份:2023
- 资助金额:48.00 万元
- 项目类别:面上项目
小脑浦肯野细胞突触异常在特发性震颤中的作用机制及靶向干预研究
- 批准号:82371248
- 批准年份:2023
- 资助金额:47.00 万元
- 项目类别:面上项目
相似海外基金
CAREER: Bridging Research & Education in Delineating Fatigue Performance & Damage Mechanisms in Metal Fused Filament Fabricated Inconel 718
职业:桥梁研究
- 批准号:
2338178 - 财政年份:2024
- 资助金额:
$ 221.7万 - 项目类别:
Standard Grant
CAREER: Understanding the Molecular Mechanisms of Insect Cuticular Chitin Maintenance
职业:了解昆虫表皮几丁质维持的分子机制
- 批准号:
2338209 - 财政年份:2024
- 资助金额:
$ 221.7万 - 项目类别:
Continuing Grant
CAREER: Leveraging Plastic Deformation Mechanisms Interactions in Metallic Materials to Access Extraordinary Fatigue Strength.
职业:利用金属材料中的塑性变形机制相互作用来获得非凡的疲劳强度。
- 批准号:
2338346 - 财政年份:2024
- 资助金额:
$ 221.7万 - 项目类别:
Continuing Grant
Conference: 2024 Thiol-Based Redox Regulation and Signaling GRC and GRS: Mechanisms and Consequences of Redox Signaling
会议:2024年基于硫醇的氧化还原调节和信号传导GRC和GRS:氧化还原信号传导的机制和后果
- 批准号:
2418618 - 财政年份:2024
- 资助金额:
$ 221.7万 - 项目类别:
Standard Grant
Elucidating mechanisms of biological hydrogen conversion through model metalloenzymes
通过模型金属酶阐明生物氢转化机制
- 批准号:
2419343 - 财政年份:2024
- 资助金额:
$ 221.7万 - 项目类别:
Standard Grant
EAGER/Collaborative Research: Revealing the Physical Mechanisms Underlying the Extraordinary Stability of Flying Insects
EAGER/合作研究:揭示飞行昆虫非凡稳定性的物理机制
- 批准号:
2344215 - 财政年份:2024
- 资助金额:
$ 221.7万 - 项目类别:
Standard Grant
Collaborative Research: Deciphering the mechanisms of marine nitrous oxide cycling using stable isotopes, molecular markers and in situ rates
合作研究:利用稳定同位素、分子标记和原位速率破译海洋一氧化二氮循环机制
- 批准号:
2319097 - 财政年份:2024
- 资助金额:
$ 221.7万 - 项目类别:
Standard Grant
CAREER: Probing structural dynamics and regulatory mechanisms of RNA-guided CRISPR-Cas12 endonucleases and their analogues
职业:探索 RNA 引导的 CRISPR-Cas12 核酸内切酶及其类似物的结构动力学和调控机制
- 批准号:
2339799 - 财政年份:2024
- 资助金额:
$ 221.7万 - 项目类别:
Continuing Grant
CAREER: Measurement of Photochemical Mechanisms, Rates, and Pathways of Radical Formation in Complex Organic Compounds
职业:测量复杂有机化合物中自由基形成的光化学机制、速率和途径
- 批准号:
2340926 - 财政年份:2024
- 资助金额:
$ 221.7万 - 项目类别:
Continuing Grant
CAREER: Early-life social environments drive behavioral and neural mechanisms of development
职业:早期社会环境驱动行为和神经机制的发展
- 批准号:
2341006 - 财政年份:2024
- 资助金额:
$ 221.7万 - 项目类别:
Continuing Grant














{{item.name}}会员




