Specification of forebrain territories: commitments and signalling.

前脑区域的规范：承诺和信号。

• 批准号: BB/E005403/1
• 负责人: Corinne Houart
• 金额: $ 52.68万
• 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: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE005403%2F1
• 关键词: Specification; forebrain; territories; commitments; signalling.

In all vertebrates, from fish to humans, the brain is formed of three main regions, the forebrain, midbrain and hindbrain. The forebrain gives rise to our cortex, in which our conscious thoughts, emotions and many of our memories reside. It also forms the eyes and the diencephalon. How the forebrain region becomes sub-divided into telencephalon (future cortex), eye and diencephalon remains a mystery. Our aim is to understand the mechanisms underlying this subdivision. A significant number of early brain malformations observed in human foetuses (for instance following viral infection in early stage of pregnancy, or more rarely indeed by genetic defects) are due to mistakes in the steps required for normal forebrain partition. Knowing the mechanisms required for normal forebrain development will therefore help understanding the cause of these human malformations. The brain comes from a simple sheet of tissue, called neural plate. This plate closes into a tube from which the most rostral end develops into the forebrain. We already discovered that some of the decisions required to divide the forebrain into specific areas are taken before the formation of the neural tube, inside the rostral neural plate. We showed that the anterior neural border (the most rostral end of the neural plate, ANB) is required for formation of the telencephalon and is a source of signalling that needs to be received by the rostral plate in order for these cells to become telencephalon and subsequently form a cortex. We also gathered preliminary results suggesting that other irreversible decisions are taken in the neural plate. These decisions are establishing the precursors for specialised areas of the diencephalon. In this proposal, we aim to identify the neural plate cell populations that are the earliest to commit to a defined diencephalic identity and to test whether these cells are sending signals potentially able to orchestrate the identities of the areas surrounding them. We will also get a profile of the different genes that are specifically expressed in each of the studied neural plate areas, in order to get insight into the molecular nature of their differences. By the end of the three years of research, we will have identified the earliest commitments leading to specific diencephalic areas and anticipate identifying some of the molecular players underlying the establishment of the diencephalic subdivisions. We also hope to identify a novel signalling centre responsible for some of the early organisation of the forebrain territory.

在所有脊椎动物中，从鱼类到人类，大脑由三个主要区域组成，前脑，中脑和后脑。前脑产生了我们的皮层，我们有意识的思想，情感和许多记忆都存在于皮层中。它还形成了眼睛和间脑。前脑区域如何被细分为端脑（未来的皮层），眼睛和间脑仍然是一个谜。我们的目的是了解这种细分的机制。在人类胎儿中观察到的大量早期脑畸形（例如在妊娠早期病毒感染后，或更罕见的遗传缺陷）是由于正常前脑分区所需步骤的错误。因此，了解正常前脑发育所需的机制将有助于理解这些人类畸形的原因。大脑来自一个简单的组织片，称为神经板。这个板关闭成一个管，从最吻端发育成前脑。我们已经发现，将前脑划分为特定区域所需的一些决定是在吻侧神经板内的神经管形成之前做出的。我们发现，前神经边界（神经板的最前端，ANB）是端脑形成所必需的，并且是需要由喙板接收的信号源，以便这些细胞成为端脑并随后形成皮质。我们还收集了初步结果，表明其他不可逆的决定是在神经板中做出的。这些决定正在为间脑的专门区域建立先驱。在这项提案中，我们的目标是确定最早承诺一个明确的间脑身份的神经板细胞群，并测试这些细胞是否正在发送信号，可能能够协调它们周围区域的身份。我们还将获得在每个研究的神经板区域中特异性表达的不同基因的概况，以便深入了解它们差异的分子性质。在三年的研究结束时，我们将确定导致特定间脑区域的最早承诺，并预计确定间脑亚部建立的一些分子参与者。我们还希望确定一个新的信号中心，负责一些前脑领土的早期组织。

项目成果

The prethalamus is established during gastrulation and influences diencephalic regionalization.

• DOI: 10.1371/journal.pbio.0050069
• 发表时间: 2007-04
• 期刊: PLoS biology
• 影响因子: 9.8
• 作者: Staudt N;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