Drosophila; development; TGF-ß signal transduction; cell signaling
In multicellular organisms, cell-cell communication involving secreted factors is an essential means by which cells influence the fates and functions of neighboring cells. My lab uses the fruit fly Drosophila as a model system and our primary focus is in understanding the roles of TGF-ß ligands both during embryonic development and metamorphosis, as well as in adult life. We are particularly interested in the molecular mechanisms underlying the diverse cellular responses triggered by TGF-ß ligands. Another interest is coordination and integration of inputs from multiple signaling pathways. While our earlier work focused on the BMP signaling pathway and its involvement in embryonic patterning and cell fate specification, our current emphasis has shifted to dissecting the activin pathway. Unlike BMPs, Drosophila activins are expressed in differentiated cells, for e.g., in the nervous system, muscle, and adipose tissue, at late stages of development. Over the last few years we have uncovered roles for activin signaling in several aspects of nervous system development and function, such as axonal pathfinding and synaptogenesis. Our current research on activin signaling is centered on two aspects: understanding how activin signaling regulates developmental timing through interactions with the steroid hormone pathway, and how activin signaling influences carbohydrate and lipid metabolism providing a key regulatory input into energy homeostasis. In parallel we have continued to work on several aspects of BMP signal-transduction. Our previous work on Schnurri (Shn) a BMP specific Smad-cofactor led to the identification of a consensus sequence that mediates BMP-dependent repression in flies. We are using a bioinformatics approach that incorporates evolutionary constraints inferred from comparisons across 12 Drosophila genomes to identify potential novel BMP target genes containing such enhancers, that are repressed by signaling, thus less amenable to identification through conventional approaches.
Künnapuu, J., Tauscher, P.M., Tiusanen, N., Nguyen, M., Löytynoja, A., Arora, K# and O. Shimmi# (2014) Cleavage of the Drosophila screw prodomain is critical for a dynamic BMP morphogen gradient in embryogenesis. Developmental Biology 389,149-59. # Corresponding Authors
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.
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 133, 4025-34. # Corresponding Authors
*These authors contributed equally to this work.
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. # Corresponding Authors
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
Developmental Biology Center