Alex Schreiber's research addresses developmental changes that take place during vertebrate metamorphosis. A single molecule, thyroid hormone, orchestrates metamorphosis in flatfishes (flounders and soles) and frogs. In contrast to the bilaterally symmetric body plan characteristic of frogs and virtually all other vertebrates, flatfish larvae metamorphose into the world's most morphologically asymmetric vertebrates: one eye translocates to the opposite side of the head, the brain and skull become asymmetrically shaped, and the fish spends the rest of its life with its eye-less side facing the ground. The direction of eye migration and left-right sidedness varies within and among species. What thyroid hormone-responsive genes mediate asymmetric craniofacial and brain remodeling during metamorphosis, and what genes establish left-right sidedness in flatfish?

These questions are being addressed using a three step approach: genes expressed during metamorphosis are cloned into cDNA libraries, identified through DNA sequencing, and screened for asymmetric expression of corresponding RNA in the skull and brain using in situ hybridization. A comparison of flatfish thyroid hormone-responsive genes with those known to mediate amphibian metamorphosis will shed light on how evolutionarily conserved metamorphosis is among phylogenetically distant vertebrate taxa. Small flatfish species from regions as geographically diverse as the Amazon River basin and the Chesapeake Bay are cultured in the lab to generate embryos for molecular and cellular manipulation.

FIGURES

left Craniofacial remodeling during summer flounder metamorphosis is characterized by the migration of the right eye to the left side of the head, as well as transition from a mostly cartilagenous (blue stain) to a largely ossified (red stain) skull. [figure courtesy of Professor Chris Rose]

above X-ray of a juvenile flounder.

below Most summer flounder larvae metamorphose into 'sinistral' (both eyes on the left side) juveniles, though a minority will exhibit reversed or'dextral' asymmetry (both eyes on the right side). The molecular basis for flatfish sidedness remains a mystery.

SELECTED PUBLICATIONS

Huang, Audrey M. (2004) Flounder: Not Just For Dinner Anymore. Spectra: The Newsletter of the Carnegie Institution.

Schreiber, A.M. and Specker, J.L. (1998). Metamorphosis in the summer flounder (Paralichthys dentatus): stage-specific developmental response to altered thyroid status. Gen. Comp. Endocrinol. 111, 156-166.

Schreiber, A.M. and Specker, J.L. (1999). Metamorphosis in the summer flounder, Paralichthys dentatus: changes in gill mitochondria-rich cells. J. Exp. Biol. 202, 2475-2484.

Schreiber, A.M., Das, B., Huang, H., Marsh-Armstrong, N., Brown D.D. (2001). Diverse developmental programs of Xenopus laevis metamorphosis are inhibited by a dominant negative thyroid hormone receptor. Proc. Natl. Acad. Sci. 98, 10739-10744.

Schreiber, A.M. and Brown, D.D. (2003). Tadpole skin dies autonomously in response to thyroid hormone at metamorphosis. Proc. Natl. Acad. Sci. 100,1769-1774.