Regulatory factor identification for nodal genes in zebrafish by causal inference

• DOI: 10.3389/fcell.2022.1047363
• Publication Date: 2022-10-20T04:44:44Z
• Authors: Cencan Xing; Zehua Zeng; Yaqi Li; Bo Gong; Weimin Shen; Roshan Shah; Lu Yan; Hongwu Du; Anming Meng
• Keywords: Nodal signaling; SOX10; Gene regulatory network

Activation of nodal genes is critical for mesoderm and endoderm induction. Our previous study reported that zebrafish ndr1 / squint ndr2 cyclops are coordinately regulated by maternal Eomesa, Hwa-activated β-catenin (Hwa/β-catenin) signaling, Nodal autoregulation (Nodal/Smad2) signaling. However, the exact contribution underlying mechanisms still elusive. Here, we applied “causal inference” to evaluate causal between independent dependent variables, found Hwa/β-catenin Smad2 cause activation, while Eomesa activation. Mechanistically, different cis -regulatory regions bound β-catenin, were screened out via ChIP-qPCR verified transgene constructs. The marginal GFP expression driven transgenesis could be diminished without both Hwa/β-catenin, not bind activate demonstrated transgenesis. Thus, distinct regulation relies on regions.