The gene regulatory basis of genetic compensation during neural crest induction

作者: Christopher M. Dooley , Neha Wali , Ian M. Sealy , Richard J. White , Derek L. Stemple

DOI: 10.1101/314534

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摘要: Background: 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 but detailed interactions within remain be resolved. Results: We have used knockout RNA sequencing strategies dissect differentiation in zebrafish. establish initiation takes place just after genome activation. genetically ablate using double mutants tfap2a;tfap2c or remove specific subsets with sox10 mitfa knockouts characterise genome-wide expression levels multiple time points. find although single allele tfap2c capable maintaining early absence tfap2a function, many target genes remains abnormal sensitive tfap2 dosage. This separation morphological molecular phenotypes identifies core set required development. Using knockouts, we associate previously uncharacterised pigment development role maternal Hippo signalling melanocyte differentiation. Conclusions: Stepwise genetic ablation module induction. work extends refines while also uncovering complex transcriptional basis compensation via paralogues.

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