Graduate Student - Ph.D.

Genetics

Harvard Medical School (Boston, MA)

Connie L. Cepko

Thyroid Hormone as a Developmental Molecule in the Global Organization and Timing of Retinal Development

Retinoic acid (RA) synthetic and degrading enzymes are patterned along the dorsoventral axis, and have been shown to play a role in retinal patterning in fish and frogs. Thyroid hormone (TH) synthetic and degradative enzymes similarly are patterned in the retina. Work in mice and humans suggest a role for TH in retinal development, and more broadly in many developing tissues. We have been investigating the roles of TH and RA in formation of retinal pattern. As well, we have investigated the roles of several transcription factors in retinal patterning. The data so far suggest that a complex set of interactions direct the formation of photoreceptor pattern. Vax appears to affect the distribution of rod photoreceptors, as does RA and TH. Effects on the cone pattern can also be seen with TH. Our work now focuses on how these genes work in what may be a complex network where they can effect each other’s level of expression. RNAi vectors that are effective against the TH synthetic and degradative enzymes, as well as the TH receptors, have been made and are being scored for their effects on retinal development. The same has been done for the RA pathway and Vax. We have made reporter constructs for signal transduction by TH and RA and these are being used to reveal where in vivo the TH and RA signals are being read. (See Sen et al., 2005 and Trimarchi et al. 2008).