Systems biology of embryonic development: Prospects for a complete understanding of the Caenorhabditis elegans embryo.

Q1 Biochemistry, Genetics and Molecular Biology
John Isaac Murray
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引用次数: 8

Abstract

The convergence of developmental biology and modern genomics tools brings the potential for a comprehensive understanding of developmental systems. This is especially true for the Caenorhabditis elegans embryo because its small size, invariant developmental lineage, and powerful genetic and genomic tools provide the prospect of a cellular resolution understanding of messenger RNA (mRNA) expression and regulation across the organism. We describe here how a systems biology framework might allow large-scale determination of the embryonic regulatory relationships encoded in the C. elegans genome. This framework consists of two broad steps: (a) defining the "parts list"-all genes expressed in all cells at each time during development and (b) iterative steps of computational modeling and refinement of these models by experimental perturbation. Substantial progress has been made towards defining the parts list through imaging methods such as large-scale green fluorescent protein (GFP) reporter analysis. Imaging results are now being augmented by high-resolution transcriptome methods such as single-cell RNA sequencing, and it is likely the complete expression patterns of all genes across the embryo will be known within the next few years. In contrast, the modeling and perturbation experiments performed so far have focused largely on individual cell types or genes, and improved methods will be needed to expand them to the full genome and organism. This emerging comprehensive map of embryonic expression and regulatory function will provide a powerful resource for developmental biologists, and would also allow scientists to ask questions not accessible without a comprehensive picture. This article is categorized under: Invertebrate Organogenesis > Worms Technologies > Analysis of the Transcriptome Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics.

胚胎发育的系统生物学:全面了解秀丽隐杆线虫胚胎的前景。
发育生物学和现代基因组学工具的融合为全面理解发育系统带来了潜力。这对于秀丽隐杆线虫的胚胎来说尤其如此,因为它的小尺寸,不变的发育谱系,以及强大的遗传和基因组工具提供了对整个生物体中信使RNA (mRNA)表达和调控的细胞分辨率理解的前景。我们在这里描述了系统生物学框架如何允许大规模确定秀丽隐杆线虫基因组编码的胚胎调控关系。这个框架包括两个大的步骤:(a)定义“部分列表”——所有细胞在发育过程中每次表达的所有基因;(b)通过实验扰动对这些模型进行计算建模和改进的迭代步骤。在通过大规模绿色荧光蛋白(GFP)报告分析等成像方法确定零件清单方面取得了实质性进展。成像结果现在正在通过高分辨率转录组方法(如单细胞RNA测序)得到增强,并且很可能在未来几年内了解胚胎中所有基因的完整表达模式。相比之下,迄今为止进行的建模和扰动实验主要集中在单个细胞类型或基因上,需要改进的方法将其扩展到完整的基因组和生物体。这种新兴的胚胎表达和调控功能的综合图谱将为发育生物学家提供强大的资源,也将使科学家能够提出没有全面图片就无法获得的问题。本文分类如下:无脊椎动物器官发生>蠕虫技术>转录组基因表达和转录层次分析>基因网络和基因组学。
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期刊介绍: Developmental biology is concerned with the fundamental question of how a single cell, the fertilized egg, ultimately produces a complex, fully patterned adult organism. This problem is studied on many different biological levels, from the molecular to the organismal. Developed in association with the Society for Developmental Biology, WIREs Developmental Biology will provide a unique interdisciplinary forum dedicated to fostering excellence in research and education and communicating key advances in this important field. The collaborative and integrative ethos of the WIREs model will facilitate connections to related disciplines such as genetics, systems biology, bioengineering, and psychology. The topical coverage of WIREs Developmental Biology includes: Establishment of Spatial and Temporal Patterns; Gene Expression and Transcriptional Hierarchies; Signaling Pathways; Early Embryonic Development; Invertebrate Organogenesis; Vertebrate Organogenesis; Nervous System Development; Birth Defects; Adult Stem Cells, Tissue Renewal and Regeneration; Cell Types and Issues Specific to Plants; Comparative Development and Evolution; and Technologies.
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