Professor, Developmental & Cell Biology
|Drosophila development; TGF-β signal transduction; cell signaling|
|URL||Arora Lab Webpage|
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-β (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.
|Publications||Ellis, J. E., Parker, J. L. Cho, J. and K. Arora. (2010) Activin signaling functions upstream of Gbb to regulate synaptic growth at the Drosophila neuromuscular junction. Developmental Biology 342, 121-33.|
|Pentek, J., Parker, J. L., Wu, A. and K. Arora. (2009) Follistatin preferentially antagonizes Activin rather than BMP signaling. Genesis 47, 261-73.|
|Yao, L-C., Phin, S., Cho, J., Rushlow, C., Arora, K. and R. Warrior#. (2008) Multiple modular promoter elements drive graded brinker expression in response to the Dpp morphogen gradient. Development 135, 2183-92.|
|Parker, J. L., Ellis, J. E., Nguyen, M. and K. Arora. (2006) The divergent TGF-ß ligand Dawdle utilizes an activin signaling pathway to influence axon guidance in Drosophila. Development 133, 4981-91.|
Yao, L-C., Blitz, I. L*., Peiffer, D. A*., Phin, S*., Wang, Y., Ogata, S., Cho, K. C., Arora, K. and R. Warrior. (2006). Schnurri transcription factors from Drosophila and vertebrates can mediate BMP signaling through a phylogenetically conserved mechanism. Development (In press).
*These authors contributed equally to this work.
|Brugger, S., Merrill, A., Torres-Vazquez, J., Wu, N., Ting, M., Cho, J., Dobias, S. L., Yi, S. E., Lyons, K., Bell, J. R., Arora, K., Warrior, R and R. Maxson. (2004). A phylogenetically conserved cis-regulatory module in the Msx2 promoter is sufficient for BMP-dependent transcription in murine and Drosophila embryos. Development 131, 5153-65.|
|Parker, J. L., Stathakis, D., and K. Arora. Regulation of BMP and Activin signaling in Drosophila. (2003) In "Progress in Molecular and Subcellular Biology", Ed. A. Beschin, Invertebrate Cytokines, Springer-Verlag, pp. 73-101.|
|Arora, K., and Warrior, R. (2001) A new Smurf in the village. Developmental Cell 1, 441-442.|
|Torres-Vazquez, J., Park, S., Warrior, R., and K. Arora. (2001). The transcription factor Schnurri plays a dual role in mediating Dpp signaling during embryogenesis. Development 128: 1657-1670.6.|
|Torres-Vazquez, J., Warrior, R., and K. Arora. (2000) schnurri is required for dpp dependant patterning of the Drosophila wing. Developmental Biology 227: 388-402.|
|Dai, H., Hogan, C., Gopalakrishnan, B., Torres-Vazquez, J., Nguyen, M., Park, S., Raftery, L. A., Warrior, R., and K. Arora. (2000). The zinc finger protein Schnurri acts as a Smad partner in mediating the transcriptional response to Decapentaplegic. Developmental Biology 227: 373-387.|
|Nguyen, M., Parker, L., and K. Arora. (2000) Identification of maverick, a novel member of the TGF-ß superfamily in Drosophila. Mechanisms of Development 95: 201-206.|
|Nguyen, M., Park, S. B., Marqués, G., and K. Arora. (1998) Interpretation of a BMP-activity gradient in Drosophila embryos depends on synergistic signaling by two type I receptors Sax and Tkv. Cell 95: 495-506.|
|Arora, K., O'Connor, M. B., and R. Warrior. (1996) BMP Signaling in Drosophila Embryogenesis. Annals of the New York Academy of Sciences 785, 80- 97.|
Arora, K., Dai, H., Kazuko, S. G., Jamal, J., O'Connor, M. B., Letsou, A., 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, 781-790.
Letsou, A., Arora, K., Wrana, J., Simin, K., Twombly, V., Jamal, J., Staehling-Hampton, K., Hoffmann, F. M., Gelbart, W. M., Massagué, J., 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, 899-908.
|Arora, K., Levine, M., 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, 2588-2601.|
|Wrana, J. L., Tran, H., Attisano, L., Arora, K., Childs, S. R., Massagué, J., and M. B. O'Connor. (1994) Two distinct transmembrane serine/threonine kinases from Drosophila form an activin receptor complex. Mol. Cell. Biol. 14, 944-950.|
|Childs, S. R., Wrana, J. L., Arora, K., Attisano, L., O'Connor, M. B., and J. (1993) Identification of a Drosophila activin receptor. Proceedings of the National Academy of Sciences 90, 9475-9479.|
|Arora, K., and C. Nüsslein-Volhard. (1992) Altered mitotic domains reveal fate map changes in Drosophila embryos mutant for zygotic dorsal ventral patterning genes. Development 114, 1003-1024.|
|Ray, R., Arora, K., Nüsslein-Volhard, C., and W. Gelbart. (1991) The control of cell fate along the dorsal - ventral axis of the Drosophila embryo. Development 113, 35-54.|
|Kosman, D., Ip, T., Levine, M., and K. Arora. (1991) The establishment of the mesoderm-neuroectoderm boundary in the Drosophila embryo. Science 254, 118-122.|
|Rushlow, C., and K. Arora. (1990) Dorsal ventral polarity and pattern formation in the Drosophila embryo. Seminars in Cell Biology 1, 137-149.|
Developmental Biology and Genetics
|Research Center||Developmental Biology Center|
|Link to this profile||http://www.faculty.uci.edu/profile.cfm?faculty_id=2684|