Developmental Tuning of Turing Patterning

在我们出生之前，我们的身体就已经安排好了自己的部分。我们身体的某些部位只有一个（如头、鼻子、脾脏），其他部位只有两个（如手臂、眼睛、大脚趾），这些部位通过相当于胚胎的全球定位系统来定位。然而，还有其他结构，如毛发或肾脏的肾单位，数量非常多，以至于无法将它们中的每一个都专门放置。相反，身体似乎用一个简单的“规则”来布置这些结构。这一“规则”涉及细胞之间的局部相互作用，以确保每个滤泡、肾元或其他结构与其他同类形成一定距离。理论生物学家已经提出并证明了可以作为这些“规则”运作基础的一般概念，分子生物学家最近的工作证实并扩展了这些理论观点，确定了设定“规则”的特定基因和蛋白质。然而，像毛囊这样的结构在全身并不是均匀的。例如，眉毛和头皮上的毛发更浓密，这标志着这些部位的皮肤不同于额头，额头上的毛发很小，很细。在这个建议中，我们的目标是理解这种模式的区别，在这种情况下，毛囊作为其他重复结构的例子，可以实现。从本质上讲，我们将在组织中上升一个层次，以了解大小和间距“规则”如何在不同的位置变化。我们将通过研究小鼠皮肤不同部位的毛囊形成来做到这一点，重点是各种胡须，因为它们的独特模式。我们的项目将结合分子生物学和细胞生物学，分析和操纵细胞之间传递的信号，并通过数学模拟来解释和指导实验。实验将主要在培养的皮肤样本上进行，避免使用完整的动物。预期的结果是在分子和概念水平上理解身体如何通过调整不同区域来利用单一模式形成系统来实现复杂的解剖结构。

Our bodies arrange their own parts appropriately before we are born. We have only one of certain body parts (e.g. head, nose, spleen) and two of others (e.g. arm, eye, big toe) of, and these achieve their position through an equivalent of an embryo's Global Positioning System. However, still other structures, like hairs or nephrons of the kidney, are very numerous - too numerous to have a dedicated placing of each and every one of them. Instead, the body seems to use a simple "rule" to lay out these structures. This "rule" involves local interactions between cells which make sure that each follicle, nephron, or other structure, forms at a set distance from others of the same kind. Theoretical biologists have provided and proven general concepts that could underlie the operation of these "rules" and recent work by molecular biologists has substantiated and extended these theoretical ideas, identifying the specific genes and proteins that act as to set the "rule".However, structures like hair follicles are not homogeneous across the body. For example, the eyebrows and scalp produce thicker hair types that mark these parts of the skin as being different from, for example, the forehead, which has very small, fine hairs. In this proposal we aim to understand how such distinctions in pattern, in this case of hair follicles serving as an example of other repeated structures, can be achieved. In essence, we will go up one level in organisation to understand how the size and spacing "rule" can be varied in different locations. This we will do by studying hair follicle formation on different parts of the mouse skin, with a focus on the various whiskers because of their distinctive pattern. Our project will be a combination of molecular and cell biology in analysing and manipulating the signals that pass between cells and mathematical simulations to interpret and guide the experimentation. Experiments will be done primarily on cultured skin samples, sparing use of intact animals. The intended outcome is to understand at both molecular and conceptual levels how the body can utilise a single pattern forming system by tuning in different regions to achieve a complex anatomy.