Dis3l2 is essential for neural crest survival by modulating Akt signaling

DIS3-like 3'-5' exoribonuclease 2 (DIS3L2), an exoribonuclease, is known to preferentially degrade uridylated RNA substrates, miRNAs, and ncRNAs. Recent reports show that DIS3L2 also plays a key role in cell proliferation and tumor growth. Mutations in DIS3L2 are associated with congenital overgrowth disorders such as Perlman syndrome, yet the developmental functions of DIS3L2 remain unknown. We report the developmental role of dis3l2 in neural crest specification, patterning, and survival in the zebrafish embryo. The dis3l2 morphants exhibited reduced expression of neural crest specifier genes coupled with extensive apoptosis in the neural tissue. Our study demonstrates that dis3l2 regulates neural tissue apoptosis and progenitor functions through the Akt-GSK3β signaling pathway. Additionally, we show that dis3l2 is essential for early mitoses in the zebrafish blastula and plays a key role in maintaining spindle length at metaphase, chromosome congression, spindle pole integrity, and cytokinesis. In summary, we identify new functions of exoribonuclease dis3l2 in cell fate specification, neural crest survival, and mitosis during embryogenesis, which form the underlying basis of DIS3L2-associated Perlman syndrome.