Epithelial bending in mammalian morphogenesis

哺乳动物形态发生中的上皮弯曲

• 批准号: BB/P007325/1
• 负责人: Jeremy Green
• 金额: $ 80.17万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FP007325%2F1
• 关键词: Epithelial; bending; mammalian; morphogenesis

Genes drive and control the embryonic development of tissues and organs of the body in the way that software drives a computer. We are beginning to understand "gene programmes" written in the genome. However, we know much less about how the software drives the hardware: how do genes drive the physical shapes that we see? This question needs to be answered if we want one day to fix the hardware using biological methods. To answer this question, the extremely complicated and elaborate process of physical construction of the body (known as "morphogenesis") needs to be broken down into more easily analysed sub-processes. One of these is the bending of a sheet of cells to make a groove or pit. This is called "invagination". Invagination is medically important because it occurs in making the brain and spinal cord and its failure is a major class of birth defects (which includes, for example, spina bifida). We propose to look at something simpler but that will give answers about several different kinds of invagination. We will examine the formation of teeth, salivary glands, hair follicles and mammary ducts ("ectodermal organs") in mice. Each of these organs begins with an invagination that becomes gradually deeper. We will use some new techniques to detect more precisely than ever before the outlines of cells that make up the invaginating sheet so that we can get good, engineering-style measurements of their structures. Finally, we can grow these tissues in a dish and see which kinds of chemical "inhibitors" (which interfere with certain known proteins in the cell) will block which parts of the morphogenesis. This will link the cell movements and shape changes to particular proteins. Since proteins come from known genes, these studies, together with the mutant studies. will link cell shapes and movements to genes and be able to fit them in with the genetic software written in the DNA. comparing multiple small organs of this type, we can get an idea of the rules that make them similar but different. Ultimately this kind of knowledge should make it possible to use chemical signals (software) to drive structural repairs (hardware).

基因驱动和控制身体组织和器官的胚胎发育，就像软件驱动计算机一样。我们开始理解写在基因组中的“基因程序”。然而，我们对软件如何驱动硬件知之甚少：基因如何驱动我们看到的物理形状？如果我们希望有一天用生物方法修复硬件，这个问题需要得到回答。要回答这个问题，需要将极其复杂和复杂的身体构造过程(称为“形态发生”)分解为更容易分析的子过程。其中之一是弯曲一片电池以形成凹槽或凹坑。这被称为“内陷”。内陷在医学上很重要，因为它发生在大脑和脊髓的形成过程中，它的失败是一种主要的出生缺陷(例如，包括脊柱裂)。我们建议看一些更简单的东西，但这将给出几种不同类型的内陷的答案。我们将研究小鼠牙齿、唾液腺、毛囊和乳腺导管(“外胚层器官”)的形成。这些器官中的每一个都从内陷开始，并逐渐变得更深。我们将使用一些新技术，比以往任何时候都更准确地检测构成内陷薄片的细胞的轮廓，这样我们就可以对它们的结构进行良好的、工程化的测量。最后，我们可以在培养皿中培养这些组织，看看哪种化学“抑制物”(干扰细胞中的某些已知蛋白质)会阻止形态发生的哪些部分。这将把细胞的运动和形状变化与特定的蛋白质联系起来。由于蛋白质来自已知基因，这些研究与突变研究一起进行。将把细胞的形状和运动与基因联系起来，并能够将它们与DNA中编写的遗传软件相匹配。比较这种类型的多个小器官，我们可以了解使它们既相似又不同的规则。归根结底，这种知识应该使使用化学信号(软件)来推动结构修复(硬件)成为可能。

项目成果

Resolving morphogenesis into quantifiable cell behaviours.

• DOI: 10.1242/dev.199794
• 发表时间: 2022-11-01
• 期刊: Development (Cambridge, England)

Epithelial invagination by vertical telescoping

垂直伸缩导致上皮内陷

• DOI: 10.1101/515981
• 发表时间: 2019
• 作者: Li J

Cellular systems for epithelial invagination.

• DOI: 10.1098/rstb.2015.0526
• 发表时间: 2017-05-19
• 期刊: Philosophical transactions of the Royal Society of London. Series B, Biological sciences
• 作者: Pearl EJ;Li J;Green JB
• 通讯作者: Green JB

Methods of Palate Culture in Later Palatogenesis: Elevation, Horizontal Outgrowth, and Fusion.

腭发育后期的腭培养方法：抬高、水平生长和融合。

• DOI: 10.1007/978-1-0716-1847-9_6
• 发表时间: 2022
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Morgan JD

Mutations in Hcfc1 and Ronin result in an inborn error of cobalamin metabolism and ribosomopathy.

• DOI: 10.1038/s41467-021-27759-7
• 发表时间: 2022-01-10
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Chern T;Achilleos A;Tong X;Hill MC;Saltzman AB;Reineke LC;Chaudhury A;Dasgupta SK;Redhead Y;Watkins D;Neilson JR;Thiagarajan P;Green JBA;Malovannaya A;Martin JF;Rosenblatt DS;Poché RA
• 通讯作者: Poché RA