Specification of forebrain territories: commitments and signalling.

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，即前脑、中脑和后脑。前脑产生了我们的大脑皮层，我们的有意识的思想、情绪和许多记忆都驻留在那里。它还形成眼睛和间脑。前脑区域如何细分为端脑(未来的皮质)、眼睛和间脑仍然是一个谜。我们的目标是了解这种细分背后的机制。在人类胎儿中观察到的大量早期脑畸形(例如，在怀孕早期受到病毒感染，或者更罕见的是由于基因缺陷)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。大脑由一张简单的组织构成，称为神经板。这块板闭合成一根管子，从管子的最远端发育到前脑。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神经管形成之前做出的，也就是在头端神经板内。我们发现，神经前缘(神经板的最远端，ANB)是端脑形成所必需的，也是需要被吻侧板接收的信号来源，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，表明神经板还做出了其他不可逆转的决定。这些决定正在为间脑的特殊区域建立先兆。在这项提议中，我们的目标是识别最早致力于确定间脑身份的神经板细胞群体，并测试这些细胞是否正在发出信号，可能能够协调它们周围区域的身份。我们还将了解在每个被研究的神经板区域中特定表达的不同基因的概况，以便深入了解它们差异的分子本质。到三年的研究结束时，我们将确定导致特定间脑区域的最早承诺，并预期确定建立间脑分区的一些分子参与者。我们还希望找到一个新的信号中心，负责前脑区域的一些早期组织。

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.