Developmental regulatory system of ocular‐side‐specific asymmetric pigmentation in flounder: Critical role of retinoic acid signaling

Abstract The body color of the Pleuronectiformes is bilaterally asymmetric between right and left halves, with a dark ocular‐side and a white blind‐side. This body color asymmetry develops by restricted differentiation of melanophores and xanthophores on the ocular‐side during metamorphosis, accompanied by migration of one eye to the future ocular‐side. In this study, we elucidated the developmental regulatory system of this lateralized pigmentation. We found that in flounder, Sox10‐positive chromatophore progenitors appear bilaterally both in the ocular‐ and blind‐side skin of metamorphosing larvae, and that those arriving at the ocular‐side skin differentiate into gch2 ‐positive chromatoblasts and then chromatophores. Transient exposure of metamorphosing larvae to retinoic acid (RA)‐induced progenitors on the blind‐side to differentiate into gch2 ‐positive chromatoblasts. On the contrary, exposure to an RA receptor antagonist, BMS493, suppressed the differentiation of gch2 ‐positive chromatoblasts on the ocular‐side. Thus, we demonstrated that RA is essential for flounder chromatophore progenitors to differentiate into chromatoblasts. At the time of chromatoblast differentiation on the ocular‐side, cyp26b1 , which inactivates RA, was upregulated on the blind‐side skin compared with the ocular‐side. Therefore, we surmise that ocular‐side‐specific pigmentation is regulated by the inhibition of RA‐signaling by cyp26b1 on the blind‐side.