Global regulatory logic for specification of an embryonic cell lineage
Global regulatory logic for specification of an embryonic cell lineage
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DOI：
10.1073/pnas.0711220105
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发表时间：
2008-04-22
影响因子：
11.1
通讯作者：
Davidson, Eric H.
中科院分区：
文献类型：
--
作者：
Oliveri, Paola;Tu, Qiang;Davidson, Eric H.
对发育过程的解释最终必须用基因组管理代码的术语来表述。胚胎细胞谱系的指定是由编码转录因子的基因之间的相互作用网络驱动的。在这里，我们提出了基因调控网络(GRN)，它指导着海胆胚胎骨骼微绒毛谱系的规范。GRN现在包括了所有在这一谱系中表达的调控基因，直到囊胚晚期，正如全基因组调查所确定的那样。通过大规模的扰动分析建立了GRN的结构，其中每个基因在GRN中的表达被吗啡切断，并定量测量了对所有其他基因的影响。几项顺势监管分析提供了额外的证据。GRN的解释能力足以为特定时期内微绒世系的所有可观察到的发育功能提供因果解释。这些功能是：(T)通过对母体局部信号的转录解释获得身份的初始；(H)使用双负门激活特定的调控基因；(Iii)通过激活反馈亚电路来动态稳定调控状态；(Iv)排除替代调控状态；(V)呈现微粒本身所需的信号以及相邻内胚层谱系发育所需的两种不同信号；以及(0)骨骼基因组的谱系特异性激活。GRN准确地预测基因表达反应，并对规范的生物学提供一致的解释。
Explanation of a process of development must ultimately be couched in the terms of the genomic regulatory code. Specification of an embryonic cell lineage is driven by a network of interactions among genes encoding transcription factors. Here, we present the gene regulatory network (GRN) that directs the specification of the skeletogenic micromere lineage of the sea urchin embryo. The GRN now includes all regulatory genes expressed in this lineage up to late blastula stage, as identified in a genomewide survey. The architecture of the GRN was established by a large-scale perturbation analysis in which the expression of each gene in the GRN was cut off by use of morpholinos, and the effects on all other genes were measured quantitatively. Several cis-regulatory analyses provided additional evidence. The explanatory power of the GRN suffices to provide a causal explanation for all observable developmental functions of the micromere lineage during the specification period. These functions are: (t) initial acquisition of identity through transcriptional interpretation of localized maternal cues; (h) activation of specific regulatory genes by use of a double negative gate; (iii) dynamic stabilization of the regulatory state by activation of a feedback subcircuit; (iv) exclusion of alternative regulatory states; (v) presentation of a signal required by the micromeres themselves and of two different signals required for development of adjacent endomesodermal lineages; and (0) lineage-specific activation of batteries of skeletogenic genes. The GRN precisely predicts gene expression responses and provides a coherent explanation of the biology of specification.