Cellular mechanisms of embryonic boundary during notochord formation in enopus

我们正在申请资金来研究胚胎组织分离的过程。新形成的组织被所谓的胚胎边界所划定，这防止了细胞混合，因此对维持胚胎的组织至关重要。对于在边界处起作用的细胞机制，我们所知甚少。了解维持组织一致性和防止不同细胞类型之间的细胞混合的机制具有普遍重要性，包括对人类疾病。事实上，这种过程在癌症转移中似乎是不受调节的，肿瘤细胞可以离开起源组织并渗透到其他组织中。我们使用早期的青蛙胚胎作为模型，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，因为没有任何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著抑制，而不会显著影响边界的正确分选，这一意外发现与广泛接受的基于细胞粘附特性的组织形成模型相矛盾。相反，我们认为细胞知道它们必须采取哪种行为（即与相似的细胞混合，而不是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。我们的目标是鉴定通过接触介导这种细胞间识别的分子，并揭示由这些信号触发的调节细胞行为的机制。

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.