GSE127795
ADAR1 mediated regulation of neural crest-derived melanocytes and Schwann cell development.
We studied the physiological requirement of A-to-I RNA editing in neural crest cells. To this end, we generated mouse lines that undergo neural crest cell-specific deletion of Adar1 making use of the HtPAcre reporter. The mutants show global depigmentation and absence of myelin within the peripheral nerves. To assess global changes in gene regulation caused by conditional Adar1 deficiency in Schwann cells, a we performed transcriptomic analysis (RNA-seq) of sciatic nerves from independent samples from three control and three mutant animals at P4. The steady-state level of 3,009 mRNAs differed by at least two-fold in abundance between the two genotypes. Analysis of the 3,009 differentially-expressed mRNAs using the interferome database showed 75% of them to be within or associated with IFN type 1 or 2 signaling pathway. Interestingly, 34% of the RNA transcripts deregulated upon Adar1 invalidation are also deregulated upon nerve injury. Overall, our results suggest that Adar1 safeguards neural crest-derived cells from unwanted MDA5-mediated interferon production and chronic Interferon stimulated genes upregulation, with implications for the human diseases caused by ADAR1 mutations and neural crest development and linked-disorders. Overall design: we performed transcriptomic analysis (RNA-seq) of sciatic nerves from independent samples from three control and three mutant animals at Post-natal day 4.