Pitx1 directly controls the core limb development program to implement hindlimb identity [RNA-Seq]

Pitx1, critical regulator of a limited hindlimb-specific gene network, targets the limb development program common to both fore- and hindlimbs in order to implement hindlimb-specific limb morphology. The gene regulatory networks governing forelimb vs. hindlimb development in mouse were investigated using expressing profiling of morphologically stage-matched e10.5 forelimbs and e11.0 hindlimbs, ChIPseq of chromatin marks, and ChIPseq of limb-specific transcription factors Pitx1 and Tbx5. The makeup of the Pitx1-directed components of the hindlimb gene network were investigated using expression profiling of Pitx1 null hindlimbs at two stages (e11.0 and e11.5).Pitx1是一类调控受限后肢特异性基因网络的关键调控因子，其通过靶向前后肢共有的肢体发育程序，以实现后肢特异性的肢体形态建成。本研究针对调控小鼠前肢与后肢发育的基因调控网络展开探究，实验方法包括：对形态学阶段匹配的小鼠胚胎10.5天（e10.5）前肢与11.0天（e11.0）后肢开展表达谱分析、染色质标记的染色质免疫共沉淀测序（ChIP-seq），以及针对肢体特异性转录因子Pitx1与Tbx5的ChIP-seq分析。此外，本研究通过对两个发育阶段（e11.0与e11.5）的Pitx1缺失型后肢进行表达谱分析，解析了后肢基因网络中受Pitx1调控的组分组成。