Research Summary

My laboratory works at the interface between signal transduction and developmental biology. The long term goal of our research is to understand how complex developmental decisions are controlled in time and space by multiple signaling pathways. Our approach involves first identifying the individual genes comprising the regulatory network, and second elucidating the complex functional relationships between the components in order to determine the critical nodes where information is integrated. Specifically, we study how nuclear events downstream of the receptor tyrosine kinase (RTK) pathway regulate cell fate specification decisions during embryonic and retinal neural development, with particular emphasis on elucidating the post-translational control mechanisms that modulate and facilitate interactions within the network. Drosophila, and in particular the fly eye, provides an unparalleled model tissue in which to study the mechanisms of signal integration both because of its experimental tractability and because a complex interplay between multiple signaling pathways regulates many aspects of its development. Furthermore, because developmental signaling mechanisms have all been highly conserved in evolution, our work elucidating the molecular circuitries used in Drosophila directly advances understanding of how cell fates are designated and maintained in all animals, and why misregulation results in cancer and disease in humans. Thus our current and long term strategy involves combining genetic, genomic, proteomic, biochemical and cell biological methodologies in order to elucidate the conserved molecular circuitries that link and coordinate signaling modules in the developing retina.

Selected Publications

Xiong E, Dabbouseh NM, Rebay I. Interactions with the abelson tyrosine kinase reveal compartmentalization of eyes absent function between nucleus and cytoplasm. Dev Cell. 2009 Feb;16(2):271-9. (PubMed)

Jemc J, Rebay I. Identification of transcriptional targets of the dual-function transcription factor/phosphatase eyes absent. Dev Biol. 2007 Oct 15;310(2):416-29. (PubMed)

Jemc J, Rebay I. The eyes absent family of phosphotyrosine phosphatases: properties and roles in developmental regulation of transcription. Annu Rev Biochem. 2007;76:513-38. Review. (PubMed)

Vivekanand, P. and I. Rebay (2006). "Intersection of signal transduction pathways and development." Annu Rev Genet 40: 139-57. (PubMed)

Mutsuddi M, Chaffee B, Cassidy J, Silver SJ, Tootle TL, Rebay I. (2005). Using Drosophila to decipher how mutations associated with human branchio-oto-renal syndrome and optical defects compromise the protein tyrosine phosphatase and transcriptional functions of eyes absent. Genetics 170: 687-95. (PubMed)

Rebay I, Silver SJ, Tootle TL. (2005). New vision from Eyes absent: transcription factors as enzymes. Trends in Genetics I21: 163-71. (PubMed)

Silver, S., and Rebay, I. (2005). Signaling circuitries in development: Insights from the RetinalDetermination Gene Network. Development 132, 3-13. (PubMed)

Vivekanand, P., Tootle, T. L., and Rebay, I. (2004). MAE, a dual regulator of the EGFR signaling pathway, is a target of the Ets transcription factors PNT and YAN. Mech Dev 121, 1469-1479. (PubMed)

Qiao, F., Song, H., Kim, C. A., Sawaya, M. R., Hunter, J. B., Gingery, M., Courey, A. J., Rebay, I., and Bowie, J. U. (2004). Derepression by Depolymerization: Structural Insights into the Regulation of Yan by Mae. Cell 118, 163-173. (PubMed)