Parameterisation of developmental networks to understand periodic patterning

遗传学的进步使我们对我们有多少基因有了一个很好的认识。由此我们可以知道有多少成分组成和维持我们的身体。然而，很明显，基因不是孤立地起作用，而是与其他基因一起作用，形成一个网络。网络作为一个整体的运作，而不是单个基因的运作，决定了组织的形状和细胞的身份。甚至在基因被分离和测序之前，人们就已经形成了关于网络相互作用的本质的想法，这种相互作用可能会推动胚胎形态的发展。大约60年前，阿兰·图灵提出，自然界中许多重复结构的例子，比如植物上交替的叶子或皮肤上毛发的间距，都可以用一组简单的相互作用的物质来解释，他称之为形态原。他意识到，如果两个形态形成因子具有相反的性质，但在不同的范围内运作，那么这个系统几乎可以从无到有地产生有序的图案。自从这项开创性的工作以来，理论家们已经将这一见解应用于广泛的生物模式，例如动物皮肤上的斑点和条纹，贝壳上的颜色模式，内部器官，如气管，甚至身体左右两侧的区别。在定义图灵假设的特定系统的“形态原”方面，理论已经开始与实验工作相符合，但到目前为止，这一领域的研究还局限于将这个或那个分子标记为形态原。为了推动这一领域的发展，我们需要(1)定义在特定组织中起作用的重要形态因子，(2)可以描述这些分子运作的数学模型，(3)对这些分子的重要特征进行一系列测量，例如它们在组织中移动的速度和它们的分子寿命。我们将对胚胎鸡皮的羽毛图案进行自下而上的综合数学和实验研究，首次充分验证图灵的想法。最近的遗传进展使我们能够确定在鸡皮中产生模式所需的关键分子，为我们提供了拼凑理解这个系统所需的关键成分。胚胎皮肤在培养过程中发育良好，使我们能够观察和操纵图案过程，并为实验提供大量材料。因此，这是一个理想的系统，可以测试我们关于更高层次的基因网络是如何运作的，从而在自然界中创造有序模式的成熟想法。

Advances in genetics have given us a good idea of how many genes we have. From this we get an idea of how many components act to make and maintain our bodies. However, it is clear that genes do not act in isolation, but act with others to form a network. The operation of the network as a whole, rather than that of an individual gene, gives tissues their shape and cells their identity. Even before genes were isolated and sequenced, ideas were formed concerning the nature of network interactions that might operate to drive the development of form in the embryo. Almost 60 years ago Alan Turing suggested that many examples of repeated strucutres in nature, such as the alternating leaves on a plant or the spacing of hairs in the skin, could be explained by a simple set of interating substances, which he called morphogens. He realised that if two morphogens have opposing properties, but operate over different ranges, then this system can produce ordered patterns out of almost nothing. Since this seminal work theoreticians have applied this insight to a wide range of biological patterns, such as spot and stripe markings on animal skin, the colour patterns on seashells, internal organs such as the trachea and even the distinction between the left and right sides of the body. Theory is beginning to meet experimental work in defining what Turing's postulated 'morphogens' might be for specific systems, but so far studies in this area have been limited to labelling this or that molecule as a morphogen. To move this field forward we need (i) a definition of the important morphogens that act in a specific tissue, (ii) a mathematical model that can describe the operation of these molecules and (iii) a set of measurements for the important characteristics of these molecules, such as the speed with which they move through tissues and the their molecular lifespan. We will perform a bottom-up integrated mathematical and experimental study of feather patterning in embryonic chicken skin to fully test Turing's idea for the first time.Recent genetic advances have allowed us to define the key molecules required to produce a pattern in the chicken skin, giving us the key components we need to piece together an understanding of this system. Embryonic skin develops well in culture, allowing us to observe and manipulate the patterning process, and provides a large amount of material for experimentation. This is therefore the ideal system in which to test our mature ideas about how higher level networks of genes operate to create ordered patterns in nature.