Kavita Arora

Ph.D., Bombay University, India, 1985
Drosophila development; TGF-* signal transduction; cell signaling
Email address: karora@uci.edu

In multicellular organisms, cell-cell communication involving secreted factors is an essential means by which cells influence the fates of neighboring cells. Members of the transforming growth factor-ß (TGF-ß) superfamily play a key role in organizing the body axis during embryogenesis in flies, frogs and mammals. We are interested in understanding the role of two TGF-ß related genes, screw (scw) and decapentaplegic (dpp), in specifying cell fate during embryonic development in the fruitfly Drosophila. Since the TGF-ß signaling pathway is evolutionarily conserved, findings from a genetically tractable organisms like Drosophila can provide insights into the mechanism of action of TGF-ß proteins in other organisms, including humans. We have cloned the scw gene and shown that although scw transcripts are ubiquitously expressed, the protein is only required in dorsal cells. It is likely that Scw may be activated in a subset of the cells where it is expressed because of its interaction with other genes involved in patterning the embryo. We are using molecular genetic tools and biochemical techniques to test how Scw activity is modulated post-translationally.

Another focus in the lab is to understand the mechanism of TGF-ß signal transduction. Despite significant progress in identifying the receptors that bind TGF-ß ligands, the mechanism by which cells transduce these signals and their cellular responses, have not been defined in any system. We have recently identified the schnurri (shn) gene as an early nuclear target in the Dpp/TGF-ß signaling pathway. Shn resembles a family of mammalian transcription factors, and is homologous to the human major histocompatibility binding proteins, MBP-1 and MBP-2. Our data indicate that shn activity rather than its transcription, is regulated by Dpp. Future experiments will center on understanding how Shn is activated in response to Dpp.

Selected Publications
Arora, K., M. Levine and M.B. O'Connor. 1994. The screw gene encodes a ubiquitously expressed member of the TGF-ß family required for specification of dorsal cell fates in the Drosophila embryo. Genes and Development 8:2588.

Letsou, A., K. Arora, J. Wrana, K. Simin, V. Twombly, J. Jamal, K. Staehling-Hampton, F.M. Hoffmann, W.M. Gelbart, J. Massagué and M.B. O'Connor. 1995. Dpp signaling in Drosophila is mediated by the punt gene product: a dual ligand binding type II receptor of the TGF-ß receptor family. Cell 80:899.

Arora, K., H. Dai, S.G. Kazuko, J. Jamal, M.B. OConnor, A. Letsou and R. Warrior. 1995. The Drosophila schnurri gene acts in the Dpp/TGF-ß signaling pathway and encodes a transcription factor homologous to the human MBP family. Cell 81:781.

Arora K, Warrior R. A new Smurf in the village. Dev Cell. 2001 Oct;1(4):441-2

Torres-Vazquez J, Park S, Warrior R, Arora K. The transcription factor Schnurri plays a dual role in mediating Dpp signaling during embryogenesis. Development. 2001 May;128(9):1657-70.

Nguyen M, Parker L, Arora K. Identification of maverick, a novel member of the TGF-beta superfamily in Drosophila.
Mech Dev. 2000 Jul;95(1-2):201-6

Nguyen M, Park S, Marques G, Arora K. Interpretation of a BMP activity gradient in Drosophila embryos depends on synergistic signaling by two type I receptors, SAX and TKV. Cell. 1998 Nov 13;95(4):495-506