Functional dissection of the master regulator of zebrafish endoderm cell fate specification Sox32/Casanova

内胚层是脊椎动物胚胎的三个主要胚层之一，对呼吸道和胃肠道以及包括肝脏和胰腺在内的所有相关器官都有重要贡献。转录因子Sox32（也被称为Casanova）的表达是导致斑马鱼内胚层命运的复杂分子级联的最后一步。Sox32被认为是内胚层规范的主要调控因子，因为突变胚胎完全缺乏内胚层，而过表达则产生异位内胚层。因此，Sox32的重要性是显而易见的，其调控输入已被广泛研究。然而，Sox32如何在分子水平上发挥作用尚不清楚，其已知的物理和遗传相互作用不足以解释其对内胚层命运的调节。本项目旨在揭示sox32介导的内胚层命运诱导的染色质水平调控机制。它将通过功能基因组学、高通量蛋白质组学、基因组编辑、生物信息学和胚胎学的结合来实现。它将为早期胚胎发生过程中关键细胞命运决定的基因调控控制提供关键见解，并可能为未来的细胞重编程方法提供信息。

Endoderm, one of the three primary germ layers of the vertebrate embryo makes major contributions to the respiratory and gastrointestinal tracts and all associated organs including the liver and pancreas. Expression of the transcription factor Sox32 (otherwise known as Casanova) is the last step in a complex molecular cascade leading to endoderm fate in zebrafish. Sox32 is considered to be the master regulator of endoderm specification since mutant embryos completely lack endoderm, while overexpression produces ectopic endoderm. The importance of Sox32 is therefore clear, and its regulatory inputs have been broadly studied. How Sox32 functions at the molecular level, however, is less well understood, and its known physical and genetic interactions are insufficient to explain its regulation of endoderm fate. This project aims to reveal the chromatin-level regulatory mechanisms underlying Sox32-mediated induction of endoderm fate. It will be achieved through a combination of functional genomics, high-throughput proteomics, genome editing, bioinformatics and embryology. It will provide key insights into gene regulatory control of a critical cell fate decision during early embryogenesis, and potentially inform future cellular reprogramming approaches.