The development of space-time specificity of cell phenotypic variation
January 16, 2019 Source: Institute of Genetics and Developmental Biology
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];“Seeking common ground while reserving differences†is an inherent attribute of all biological processes. Gene expression, cell behavior, developmental processes, and morphological structures among individuals with the same genotype showed a certain degree of variation under the premise of general agreement. Most of the current research focuses on the analysis of "same", that is, how the average behavior of molecules or cells is regulated, while the understanding of "different", that is, the degree of phenotypic variation, the characteristics, meaning and regulation are relatively scarce. Cells are the basic unit of structure and function of organisms. Resolving phenotypic variation at the cellular level is indispensable for understanding the basic regulation of biological processes.
The developmental process of nematodes is highly comparable at the single-cell level, and the developmental behavior of the cells also exhibits a certain degree of variability, providing an ideal model for analyzing phenotypic variability at the cellular level. The Rhododendron Research Group of the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences focused on the spatial localization phenotype of cells in embryos, using long-term in vivo imaging and real-time cell tracking methods to systematically quantify embryonic development from the 4-cell stage to the 350-cell stage. The 3D localization of each cell and its degree of variation between normal individuals. Is the variation in the cellular localization phenotype associated with the developmental characteristics of the cell? The results show that the level of phenotypic variation is not random, but rather a strong determinism, influenced by the internal and external characteristics of the cells. The level of variation is regulated by the cell's developmental lineage and is associated with multiple characteristics of the cell: cells localized in similar regions of the embryo, cells in physical contact with each other, and left-right symmetrically arranged cells tend to have a more similar phenotype. The level of variation. Therefore, cell phenotypic variation is deterministic and spatially specific. Is the variation in the cellular localization phenotype time specific? The study found that with developmental advancement, almost all phenotypic variability of cells showed a highly consistent "low-high-low" temporal variation: in the early stages of development, the degree of variation was low, followed by gradual accumulation and peaking in the early and mid-term embryos, after which The embryonic global and active positional variation is down-regulated, and the degree of cell positional variation is basically restored to the early stage of development. Therefore, cell phenotypic variation is subject to strict timing regulation. Which developmental processes and regulatory molecules are involved in regulating cell positional variation? Data simulation combined with gene interference showed that the degree of variation was strictly negatively regulated at all stages of embryonic development, especially during cell division. The process of determining the precursor cell fate that occurs in the early and middle stages of the embryo drives the systematic downregulation of the system. It is speculated that fate determines the “collection†of cells, directs the cells to localize in specific regions to reduce variation, and the process provides a buffer phenotype. The strategy of variation. At the molecular level, cell adhesion and gap junction molecules are involved in defining the extent of cellular localization phenotypic variation. In summary, the study preliminarily revealed the spatiotemporal characteristics of cell phenotypic variation during normal development of the living body, and hoped to provide a reference for understanding developmental phenotypic variation and consistency maintenance at the cellular level.
The research results were published online in the Cell Reports magazine on January 8, 2019. The Du Fu research group has graduated from the master student Li Xiaoyu and the doctoral student Zhao Zhiguang as the co-first author of the paper. Du Fu is the author of the communication. The research was supported by the National Natural Science Foundation of China and the pilot project of the Chinese Academy of Sciences.
Figure: Developmental space-time specificity of embryonic cell localization phenotypic variation
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