Identification of TBX3 and shared HAND2-TBX3 target gene in early mouse limb buds [RNA-seq]

ChIP-seq is combined with RNA-seq analysis to identify the TBX3 and HAND2 target genes during mouse limb bud development. This analysis identifies the DEGs and direct transcriptional targets of HAND2 and TBX3 during the early determinative period critical to establishment of limb axis polarity and the SHH signaling center in the posterior limb bud mesenchyme. In particular, bioinformatics analysis identifies the target gene networks that are co-regulated by both TBX3 and HAND2 transcription factors in the limb bud mesenchyme. A significant fraction of the target genes identified are required for normal limb bud development and their spatio-temporal expression patterns are changed in mutant limb buds at early stages. This project was supported by SNSF Grant 310030_184734 to Rolf Zeller (project partner: Aimee Zuniga). RNA-seq analysis of a) Hand2-deficient and b) Tbx3-deficient mouse forelimb buds染色质免疫共沉淀测序（ChIP-seq）与RNA测序（RNA-seq）联合分析，用于鉴定小鼠肢芽发育过程中TBX3与HAND2的靶基因。本分析鉴定了在肢轴极性建立以及后肢芽间充质中音猬因子（SHH）信号中心形成关键的早期决定阶段内，HAND2与TBX3的差异表达基因（DEGs）及直接转录靶标。尤为重要的是，生物信息学分析鉴定了肢芽间充质中由TBX3与HAND2转录因子共同调控的靶基因调控网络。所鉴定的靶基因中有相当一部分对于正常肢芽发育是必需的，且在早期突变肢芽中它们的时空表达模式发生改变。本项目由瑞士国家科学基金会（SNSF）资助，项目编号为310030_184734，资助对象为Rolf Zeller（项目合作者：Aimee Zuniga）。本研究包含针对a）Hand2基因缺陷小鼠与b）Tbx3基因缺陷小鼠前肢芽的RNA测序分析。