A gene regulatory network anchored by LIM homeobox 1 for embryonic head development
A gene regulatory network anchored by LIM homeobox 1 for embryonic head development
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由 LIM 同源框 1 锚定的胚胎头部发育基因调控网络
DOI：
10.1002/dvg.23246
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发表时间：
2018
期刊：
影响因子：
1.5
通讯作者：
Nicolas Fossat
中科院分区：
文献类型：
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作者：
Tennille Sibbritt;Chi K. Ip;Poh‐Lynn Khoo;Emilie Wilkie;Vanessa Jones;Jane Q. J. Sun;Joanne X. Shen;Guangdun Peng;Jing‐Dong J. Han;Naihe Jing;Pierre Osteil;Mirana Ramialison;Patrick P. L. Tam;Nicolas Fossat
胚胎头的发育是由转录因子基因调控网络的活性驱动的。LHX1是一种同源盒转录因子，在胚胎头的形成中起重要作用。LHX1功能缺失导致胚胎前截短，这是由于组织前体形态发生运动中断和WNT信号活性失调所致。对Lhx1突变体胚胎的基因表达模式分析显示，前胚层的组织获得了后胚层的组织特征，这表明Lhx1的活性是头前体组织分配和模式形成所必需的。在这里，我们以LHX1为切入点，描绘了其转录靶点和相互作用物，并构建了LHX1锚定的基因调控网络。使用功能增益方法，我们确定了立即响应Lhx1激活的基因。结合已发表的非洲爪蟾胚胎LHX1 (Xlim1) ChIP‐seq数据，对小鼠头褶期胚胎前组织中LHX1响应基因和表达基因的数据集进行Meta分析，确定了LHX1的转录靶点和一系列在小鼠胚胎头形成过程中共同起作用的遗传决定因素。
Development of the embryonic head is driven by the activity of gene regulatory networks of transcription factors. LHX1 is a homeobox transcription factor that plays an essential role in the formation of the embryonic head. The loss of LHX1 function results in anterior truncation of the embryo caused by the disruption of morphogenetic movement of tissue precursors and the dysregulation of WNT signaling activity. Profiling the gene expression pattern in the Lhx1 mutant embryo revealed that tissues in anterior germ layers acquire posterior tissue characteristics, suggesting LHX1 activity is required for the allocation and patterning of head precursor tissues. Here, we used LHX1 as an entry point to delineate its transcriptional targets and interactors and construct a LHX1‐anchored gene regulatory network. Using a gain‐of‐function approach, we identified genes that immediately respond to Lhx1 activation. Meta‐analysis of the datasets of LHX1‐responsive genes and genes expressed in the anterior tissues of mouse embryos at head‐fold stage, in conjunction with published Xenopus embryonic LHX1 (Xlim1) ChIP‐seq data, has pinpointed the putative transcriptional targets of LHX1 and an array of genetic determinants functioning together in the formation of the mouse embryonic head.