Control of Cell-Cell interactions in Forebrain Morphogenesis.

前脑形态发生中细胞间相互作用的控制。

• 批准号: BB/L022303/1
• 负责人: Corinne Houart
• 金额: $ 62.51万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL022303%2F1
• 关键词: Control; Cell; interactions; Forebrain; Morphogenesis.

In human, between 2 and 3% of babies are born with birth defects; half of these suffering of mild to severe brain and/or eye impairments. In 40% of these, brain defect is accompanied by changes in brain and/or eye size. Understanding the source of these severe brain and eye conditions in new-born is a pre-requisite to plan therapeutic avenues. We found that mistakes in the very early separation between telencephalon (forming the future brain hemispheres) and eye, leads to abnormalities in brain and eye size in the animal model used in our lab (the zebrafish). This finding open the possibility that some of the pathologies related to microcephaly (smaller brain) or macrocephaly (bigger brain) may originate from early segregation defects. We very recently identified four key players in the process of separation between telencephalon and eye but have very little knowledge of how they act and how they connect to each other. In this proposal our goals are to:- Understand the exact nature of events required for correct separation of telencephalon and eye in fish and mouse.- Characterize the extent of brain and eye abnormalities induced by impaired brain/eye separation- Identify the conserved molecular interactions that are orchestrating the separation process. In completion of this programme of research, we will have identified the conserved cellular events driving normal formation of telencephalon and eye in vertebrates and established a model of functional molecular network controlling this process. We will also have linked our finding to human genetics and associated genes of the network to specific human brain malformations, strengthening the potential relation between tissue segregation defect and human developmental brain disorders.

在人类中，2%到3%的婴儿出生时就有缺陷；其中一半患有轻微到严重的大脑和/或眼睛损伤。在这些人中，40%的人大脑缺陷伴随着大脑和/或眼睛大小的变化。了解新生儿这些严重的大脑和眼睛疾病的来源是计划治疗途径的先决条件。我们发现，在我们实验室使用的动物模型(斑马鱼)中，端脑(形成未来的大脑半球)和眼睛之间非常早期的分离错误会导致大脑和眼睛大小的异常。这一发现开启了一种可能性，即与小头畸形(较小的大脑)或大头畸形(较大的大脑)相关的一些病理可能起源于早期的隔离缺陷。我们最近发现了端脑和眼睛分离过程中的四个关键角色，但对它们如何起作用以及它们如何相互联系知之甚少。在这项建议中，我们的目标是：-了解鱼类和小鼠端脑和眼睛正确分离所需事件的确切性质。-表征大脑/眼睛分离受损引起的大脑和眼睛异常的程度-确定协调分离过程的保守的分子相互作用。在完成这项研究的过程中，我们将确定驱动脊椎动物端脑和眼睛正常形成的保守细胞事件，并建立控制这一过程的功能分子网络模型。我们还将把我们的发现与人类遗传学和该网络的相关基因与特定的人类大脑畸形联系起来，加强组织分离缺陷与人类发育性大脑疾病之间的潜在联系。

项目成果

The Birth of the Eye Vesicle: When Fate Decision Equals Morphogenesis.

• DOI: 10.3389/fnins.2018.00087
• 发表时间: 2018
• 期刊: Frontiers in neuroscience
• 影响因子: 4.3
• 作者: Giger FA;Houart C
• 通讯作者: Houart C

Pineal progenitors originate from a non-neural territory limited by FGF signalling.

松果体祖细胞起源于受 FGF 信号传导限制的非神经区域。

• DOI: 10.1242/dev.171405
• 发表时间: 2019
• 期刊: Development (Cambridge, England)
• 作者: Staudt N