What genes and genetic cross-talk lead to flatfish asymmetry ???

Flatfish have the most extreme asymmetric body morphology of any vertebrates. During metamorphosis –– one eye migrates to the contralateral side of the skull, and this migration is accompanied by extensive craniofacial transformations and simultaneous development of body pigmentation that is vastly different on one side versus the other side. Flatfish therefore have both eyes on one side of their head!

The evolution of this developmental and physiological innovation remains intriguing and mysterious. Comparative genomics of two flatfish and transcriptomic analyses during metamorphosis point to roles for thyroid hormone and retinoic acid signaling, as well as phototransduction pathways. In the attached report, authors demonstrate that retinoic acid is critical in establishing asymmetric pigmentation and, via cross-talk with thyroid hormones, in modulating eye migration.

The (unexpected) involvement of visual opsins expression –– from the phototransduction pathway in the skin –– implies that illumination differences (between the two sides of the developing skull) are transmitted as “an environmental signal”, and this signal generates a retinoic acid gradient, which ultimately underlies induction of the asymmetry. Authors conclude that “identifying the genetic underpinnings of this unique developmental process answers long-standing questions about the evolutionary origin of asymmetry, and it also provides insight into the mechanisms that control body shape in vertebrates.”


Nat Genet  Jan 2o17; 49: 119-124

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