Cellular mechanisms of embryonic boundary during notochord formation in enopus

脊索形成过程中胚胎边界的细胞机制

• 批准号: 261679-2007
• 负责人: Fagotto, François
• 金额: $ 2.55万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=366450
• 关键词: Cellular; mechanisms; embryonic; boundary; during

We are requesting funds to study the process of separation of embryonic tissues. Newly formed tissues become delineated by so-called embryonic boundaries, which prevents cell mixing and are thus crucial to maintain theorganization of the embryo. Very little is known about the cellular mechanisms at work at the boundary. Understanding the mechanisms that maintain the coherence of a tissue and prevent cell mixing between different cell types is of general importance, including for human disease. Indeed, such processes appear to be de-regulated in cancer metastasis, where tumor cells can leave the tissue of origin and penetrate other tissues. We use the early frog embryo as a model, because it is easily accessible to experimentation and inexpensive. Most molecules are very similar between frogs and humans, and results obtained in our model can be readily used in other, medically relevant, model systems. In the previous granting period, we have been able to visualize directly cells while in the process of sorting, i.e. moving to the correct side of the boundary. We have discovered that that cells can still cross the boundary several hours after its formation, demonstrating that this structure is surprisingly permeable to cell migration, underscoring the importance of cells acquiring and maintaining the precise tissue identity, since no physical barrier would otherwise be able to prevent them to entering the wrong tissue. We have also observed that the strength of the adhesiveness of a cell toward its neighbors can be significantly inhibited without affecting significantly the proper sorting at the boundary, an unexpected finding that contradicts a widely accepted model for tissue formation based on the adhesive properties of cells. Instead, we propose that cells know which behavior they have to adopt (i.e. mixing with similar cells, but not with cells from a different tissue) thanks to surface sensors that detect the identity of neighboring cells. Our goal is to identify the molecules that mediate such cell to cell recognition by contact, and to unravel the mechanisms triggered by these signals that regulate the cell behavior.

我们正在申请资金来研究胚胎组织的分离过程。新形成的组织由所谓的胚胎边界界定，这阻止了细胞混合，因此对于维持胚胎的组织至关重要。对于边界上起作用的细胞机制知之甚少。了解维持组织一致性和防止不同细胞类型之间细胞混合的机制具有普遍重要意义，包括对于人类疾病。事实上，这种过程似乎在癌症转移中失调，肿瘤细胞可以离开起源组织并渗透到其他组织。我们使用早期青蛙胚胎作为模型，因为它易于实验且价格低廉。青蛙和人类之间的大多数分子非常相似，在我们的模型中获得的结果可以很容易地用于其他医学相关的模型系统。在之前的授权期间，我们已经能够在排序过程中直接可视化细胞，即移动到边界的正确一侧。我们发现，细胞在形成后几个小时仍然可以穿过边界，这表明这种结构对细胞迁移具有惊人的渗透性，强调了细胞获得和维持精确组织身份的重要性，因为没有物理屏障能够阻止它们进入错误的组织。我们还观察到，细胞对其邻居的粘附强度可以被显着抑制，而不会显着影响边界处的正确排序，这是一个意想不到的发现，与基于细胞粘附特性的广泛接受的组织形成模型相矛盾。相反，我们建议细胞知道它们必须采取哪种行为（即与相似的细胞混合，但不与来自不同组织的细胞混合），这要归功于检测相邻细胞身份的表面传感器。我们的目标是识别通过接触介导细胞间识别的分子，并揭示这些信号触发的调节细胞行为的机制。