Proliferating cells in suborbital tissue drive eye migration in flatfish

Abstract

The left/right asymmetry of adult flatfishes (Pleuronectiformes) is remarkable given the external body symmetry of the larval fish. The best-known change is the migration of their eyes: one eye migrates from one side to the other. Two extinct primitive pleuronectiformes with incomplete orbital migration have again attracted public attention to the mechanism of eye migration, a subject of speculation and research for over a century. Cranial asymmetry is currently believed to be responsible for eye migration. Contrary to that hypothesis, we show here that the initial migration of the eye is caused by cell proliferation in the suborbital tissue of the blind side and that the twist of frontal bone is dependent on eye migration. The inhibition of cell proliferation in the suborbital area of the blind side by microinjected colchicine was able to prevent eye migration and, thereafter, cranial asymmetry in juvenile Solea senegalensis (right sideness, Soleidae), Cynoglossus semilaevis (left sideness, Cynoglossidae), and Paralichthys olivaceus (left sideness, Paralichthyidae) with a bottom-dwelling lifestyle. Our results correct the current misunderstanding that eye migration is driven by the cranial asymmetry and simplify the explanation for broken left/right eye-symmetry. Our findings should help to focus the search on eye migration-related genes associated with cell proliferation. Finally, a novel model is proposed in this research which provides a reasonable explanation for differences in the migrating eye between, and sometimes within, different species of flatfish and which should aid in our overall understanding of eye migration in the ontogenesis and evolution of Pleuronectiformes.

Flatfishes, Turtles, and Bolyerine Snakes: Evolution by Small Steps or Large, or Both?

“…Very recently (Bao et al 2011) proposed that pressure of the accumulating fibroblast cells beneath the migratory eye were the direct cause of the eye's relocation, consistent with interpretations made by Okada et al (2001) and Saele et al (2006). In their study Bao et al (2011) microinjected colchicine into the suborbital region, the presumed site of the initial formation of the pseudomesial-bar rudiment, to inhibit fibroblast proliferation.…”

“…Relative to the controls, the eye of the colchicine-treated fishes either did not change location, or did so in varying degrees. Bao et al (2011) note that in no case did a treated larva show eye migration past the dorsal midline of the head. In all the cases described by Okada, Saele, and Bao and their coworkers the pseudomesial bar, or its enlarging anlage, plays a major role in eye migration.…”

“…The development of the asymmetrical distortion of the flatfish head was studied early in the 20th century (see Saele et al 2006), and has attracted the attention of a number of workers since then (e.g . Brewster 1987; Keefe and Able 1993;Lagardere et al 1993;Wagemans et al 1998;Okada et al 2001Okada et al , 2003aSasaki and Yamashita 2003;Saele et al 2004Saele et al , 2006Tagawa and Aritaki 2005;Hoshino 2006;Schreiber 2006;and Bao et al 2011). From the symmetrical larval stage one eye remains stationary, while the other migrates upward to the top of the head, and continues over onto the other side, to lie next to the static eye.…”

“…In their study Bao et al (2011) microinjected colchicine into the suborbital region, the presumed site of the initial formation of the pseudomesial-bar rudiment, to inhibit fibroblast proliferation. It should be noted that colchicine is also known to inhibit osteoblast formation (Salai et al 2001).…”

Identification and characterization of IL-1 receptor-associated kinase-4 (IRAK-4) in half-smooth tongue sole Cynoglossus semilaevis

“…Unlike other teleost fish, flatfishes undergo metamorphosis, which arises from a series of regulated processes including tissue differentiation, eye migration and other biochemical, molecular or physiological changes. After metamorphosis, C. semilaevis transform into sexually immature juveniles, possessing most of the characteristics of adult fish [28,29]. In previous studies, we also detected down-regulated expression of TLR9, MyD88 and IL-1b during metamorphosis.…”