Alk and Ltk ligands are essential for iridophore development in zebrafish mediated by the receptor tyrosine kinase Ltk

Significance Receptor tyrosine kinases (RTKs) and their stimulatory ligands regulate a variety of cellular processes. Many diseases, including cancer, are driven by mutations in or dysregulation of RTKs and their signaling pathways. The physiological ligands responsible for activating the RTKs, ALK and LTK, remained elusive. Recently, the ligands of each were identified and named “ALKAL1” and “ALKAL2” (“FAM150” or “augmentors”). Here, we demonstrate that zebrafish contain three distinct ligand molecules and describe their role in controlling pigment development in the embryo and adult zebrafish eye and body. These experiments show that these hormone-like molecules are critical factors influencing neural crest cell differentiation and progenitor/stem cell fates in zebrafish, suggesting a role for augmentors in control of similar processes in higher organisms.