Developmental control system of asymmetry of eye-sidedness and body coloration in flatfishes, and the mechanism that induces abnormality in the asymmetry development

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We investigated the developmental mechanism that controls external asymmetry of flatfish (eye location and skin pigmentation). It was demonstrated that the Nodal signaling pathway (NSP), which is known to control the sidedness of internal organs and neural circuit of habenulae, fixes the eye-sidedness by controlling the forebrain asymmetry formation. The dextral and sinistral flatfishes are segregated by the opposite asymmetry formation at the habenulae and optic chiasma under the control of the NSP.It was found that the precursors of adult-type melanophores that locate at the base of dorsal fin migrate in the myoseptum toward both left and right lateral sides. The asymmetry of skin pigmentation is established by the maturation of precursors to chromatoblasts during the migration in the myoseptum of the ocular side. Exposure to retinoic acid (RA) induces maturation of the precursors also in the ocular side, resulting in the coloration of blind side skin.