Regulation of tissue remodeling during post-embryonic development
- 5123 Rennebohm Hall
- Ph.D., California Institute of Technology, Postdoctoral Research: University of Utah
- Research Interests
- Regulation of tissue remodeling during post-embryonic development
- Research Fields
- Disease Biology, Cell Biology, Developmental Genetics, Drosophila
Development after embryogenesis often requires remodeling of existing tissues. This tissue remodeling is accomplished through carefully orchestrated changes in cell shape, movement, growth and death. Tissue repair and regeneration also require activation of remodeling mechanisms. However, how these distinct cellular processes are coordinated during tissue remodeling remains poorly understood. We study the genetic control of Drosophila metamorphosis, a stage when tissue remodeling transforms a crawling larva into a flying adult. We have identified hundreds of lethal mutations that specifically disrupt metamorphosis. Among these mutations, we have selected those required for proper control of growth and death. Most of these metamorphosis-specific mutations map to novel genes, suggesting that studying these genes will provide new insights into the regulation of tissue development and homeostasis.
Caspases during tissue remodeling: Caspases, the enzymatic executioners of apoptosis, also regulate a number of non-apoptotic functions, including cell shape, movement and growth. Both apoptotic and non-apoptotic functions of caspases are critical for tissue remodeling during metamorphosis, and inappropriate regulation of caspase activity plays a central role in many human disorders. However, the mechanisms that determine the biological outcome of caspase activation remain poorly understood. We have identified a number of novel regulators of caspase activation and are using mutations in these genes to understand how caspases coordinate tissue remodeling.
Regulating explosive tissue growth: About a day before the onset of metamorphosis, cells destined to become many of the future adult tissues start dividing at an exponential rate. Then, just as abruptly, this explosive growth phase ends, establishing the final size of these tissues. We have identified a large number of mutations that disrupt the start or end of this exponential growth phase. The genes disrupted by these mutations likely encode tumor-promotors and suppressors, respectively. We are currently characterizing the function of several novel and evolutionarily-conserved genes identified in these genetic screens.
Post-transcriptional control of hormone action: Tissue remodeling during metamorphosis is initiated by discrete pulses of steroid hormones. Steroid hormones are also responsible for triggering tissue remodeling during human puberty. A subset of the metamorphosis-specific mutations disrupt steroid hormone action. We are currently studying novel post-transcriptional mechanism that help refine global hormonal cues into specific biological responses. Human homologs of the genes involved in this pathway are critical for viral infectivity and tumorigenesis.
Search PubMed for more publications by Arash Bashirullah
Kang, Y. and A. Bashirullah (2014). A steroid-controlled global switch in sensitivity to apoptosis during Drosophila development. Developmental Biology, 386(1): 34-41.
Ihry, R.J. and A. Bashirullah (2014). Genetic control of specificity to steroid-triggered responses in Drosophila. Genetics, 196(3): 767-80.
Neuman, S.D., Ihry, R.J., Gruetzmacher, K.M. and A. Bashirullah (2014). INO80-dependent regression of ecdysone-induced transcriptional responses regulates developmental timing in Drosophila. Developmental Biology, 387(2): 229-39.
Sapiro, A.L., Ihry, R.J., Buhr, D.L., Konieczko, K.M., Ives, S.M., Engstrom, A.K., Wleklinski, N.P., Kopish, K.J. and A. Bashirullah (2013). Rapid recombination mapping for high-throughput genetic screens in Drosophila. G3, 3(12): 2313-2319.
Ihry, R.J., Sapiro, A.L. and A. Bashirullah (2012). Translational control by DEAD box RNA helicase belle regulates ecdysone-triggered transcriptional cascades. PLoS Genetics, 8(11):e1003085.