The gene regulatory basis of genetic compensation during neural crest induction

摘要: The neural crest (NC) is a vertebrate-specific cell type that contributes to wide range of different tissues across all three germ layers. gene regulatory network (GRN) responsible for the formation conserved vertebrates. Central induction NC GRN are AP-2 and SoxE transcription factors. robustness ensured through ability some these factors compensate loss function family members. However events underlying compensation poorly understood. We have used knockout RNA sequencing strategies dissect in zebrafish. genetically ablate using double mutants tfap2a;tfap2c or remove specific subsets with sox10 mitfa knockouts characterise genome-wide expression levels multiple time points. find single wild-type allele tfap2c capable maintaining early differentiation absence tfap2a function, but many target genes abnormal therefore show sensitivity reduced tfap2 dosage. This separation morphological molecular phenotypes identifies core set required development. also identify 15 somites stage as peak phenotype which strongly diminishes at 24 hpf even becomes more apparent. Using knockouts, we associate previously uncharacterised pigment development establish role maternal Hippo signalling melanocyte differentiation. work extends refines while uncovering transcriptional basis genetic via paralogues.