Parameterisation of developmental networks to understand periodic patterning

发育网络参数化以理解周期性模式

• 批准号: BB/J017183/1
• 负责人: Denis Headon
• 金额: $ 43.23万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FJ017183%2F1
• 关键词: Parameterisation; developmental; networks; understand; periodic

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.

遗传学的进步使我们对我们有多少基因有了一个很好的了解。由此，我们可以了解到有多少组成部分起着制造和维持我们身体的作用。然而，很明显，基因并不是孤立地发挥作用，而是与其他基因一起发挥作用，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，赋予了组织它们的形状和细胞它们的身份。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性质的想法，这些网络相互作用可能会驱动胚胎中的形式发展。大约60年前，艾伦·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，可以用一组简单的相互作用的物质来解释，他称之为形态发生素。他意识到，如果两种形态发生素具有相反的性质，但在不同的范围内起作用，那么这个系统几乎可以从无到有地产生有序的图案。自从这一开创性的工作以来，理论家们已经将这种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标记，贝壳上的颜色图案，气管等内部器官，甚至身体左右两侧之间的区别。理论开始满足实验工作，定义图灵假设的“形态发生素”可能是特定的系统，但到目前为止，这方面的研究仅限于将这个或那个分子标记为形态发生素。为了推动这一领域的发展，我们需要（i）对在特定组织中起作用的重要形态发生素的定义，（ii）可以描述这些分子的操作的数学模型，以及（iii）对这些分子的重要特征的一组测量，例如它们在组织中移动的速度和它们的分子寿命。我们将对鸡胚皮肤上的羽毛图案进行自下而上的综合数学和实验研究，以首次全面测试图灵的想法。最近的遗传学进展使我们能够定义在鸡皮肤上产生图案所需的关键分子，为我们提供了理解这个系统所需的关键组件。胚胎皮肤在培养中发育良好，使我们能够观察和操纵图案形成过程，并为实验提供了大量材料。因此，这是一个理想的系统，可以用来测试我们关于更高层次的基因网络如何在自然界中创造有序模式的成熟想法。

项目成果

Maintenance of distinct melanocyte populations in the interfollicular epidermis.

• DOI: 10.1111/pcmr.12375
• 发表时间: 2015-07
• 期刊: Pigment cell & melanoma research
• 影响因子: 4.3
• 作者: Glover JD;Knolle S;Wells KL;Liu D;Jackson IJ;Mort RL;Headon DJ
• 通讯作者: Headon DJ

The interfollicular epidermis of adult mouse tail comprises two distinct cell lineages that are differentially regulated by Wnt, Edaradd, and Lrig1.

• DOI: 10.1016/j.stemcr.2013.04.001
• 发表时间: 2013
• 期刊: STEM CELL REPORTS
• 影响因子: 5.9
• 作者: Gomez, Celine;Chua, Wesley;Miremadi, Ahmad;Quist, Sven;Headon, Denis J.;Watt, Fiona M.
• 通讯作者: Watt, Fiona M.

Cells or signals: which moves to drive skin pattern formation?

细胞或信号：哪个动作驱动皮肤图案的形成？

• DOI: 10.1111/exd.12270
• 发表时间: 2013
• 期刊: Experimental dermatology
• 影响因子: 3.6
• 作者: Headon D

A genome-wide association study identifies multiple loci for variation in human ear morphology.

• DOI: 10.1038/ncomms8500
• 发表时间: 2015-06-24
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Adhikari, Kaustubh;Reales, Guillermo;Smith, Andrew J. P.;Konka, Esra;Palmen, Jutta;Quinto-Sanchez, Mirsha;Acuna-Alonzo, Victor;Jaramillo, Claudia;Arias, William;Fuentes, Macarena;Pizarro, Maria;Barquera Lozano, Rodrigo;Macin Perez, Gaston;Gomez-Valdes, Jorge;Villamil-Ramirez, Hugo;Hunemeier, Tabita;Ramallo, Virginia;Silva de Cerqueira, Caio C.;Hurtado, Malena;Villegas, Valeria;Granja, Vanessa;Gallo, Carla;Poletti, Giovanni;Schuler-Faccini, Lavinia;Salzano, Francisco M.;Bortolini, Maria-Catira;Canizales-Quinteros, Samuel;Rothhammer, Francisco;Bedoya, Gabriel;Calderon, Rosario;Rosique, Javier;Cheeseman, Michael;Bhutta, Mahmood F.;Humphries, Steve E.;Gonzalez-Jose, Rolando;Headon, Denis;Balding, David;Ruiz-Linares, Andres
• 通讯作者: Ruiz-Linares, Andres

Hair Follicle Bulge Stem Cells Appear Dispensable for the Acute Phase of Wound Re-epithelialization.

• DOI: 10.1002/stem.2289
• 发表时间: 2016-05
• 期刊: Stem cells (Dayton, Ohio)
• 作者: Garcin CL;Ansell DM;Headon DJ;Paus R;Hardman MJ
• 通讯作者: Hardman MJ