Neural crest cells (NCC) are an embryonic cell population that differentiates into many tissues including e.g. heart, pigment cells, neurons, and craniofacial skeleton. Unique to the vertebrates like fish and humans, the neural crest forms along the dorsal neural tube before migrating throughout the embryonic body. The endothelin (Edn) signaling system is a key molecular regulator in cell fate determination, migration, and differentiation into different NCC derivatives. Endothelin peptide ligands and their respective G-protein coupled receptors make up the bona fide endothelin system, which newly evolved in a vertebrate ancestor. Vertebrate whole genome duplication events have then led to varying sets of Edn ligand and receptor genes among vertebrate lineages. Here, our objective is to better understand the developmental role of the five Edn ligands in the teleost fish zebrafish, Danio rerio following a teleost-specific whole genome duplication. Currently, the functional spectrum of most Edn ligands remains unknown. We used CRISPR-Cas9 genome editing to successfully knock out edn2a, edn2b, edn3a, edn3b, and edn4 genes and combine them in a zebrafish endothelin quintuple mutant line. Interestingly, we have not yet detected any observable phenotypes in this mutant line beyond the known edn3a/end3b double mutant pigmentary defects, suggesting that the endothelin system acts in a highly redundant manner. The findings of this study enhance our understanding of the functions of the endothelin ligand gene family and provide insight into the evolutionary fates of paralogous genes following whole genome duplication.