1960 East West Road, BioMed A101
Honolulu, HI 96822
Genetic and hormonal regulation of nervous system development
My laboratory studies the genetic and hormonal regulation of nervous system development in the fruit fly Drosophila melanogaster. We are particularly interested in understanding how developmental signals such as hormones, nuclear receptors, trophic factors and synaptic contacts regulate gene expression to control nervous system development and function.
One project in the lab focuses on the regulation of programmed cell death, or apoptosis, in the nervous system. In Drosophila, the genes reaper, grim and head involution defective (hid) induce apoptosis when expressed at high levels. We have identified two distinct sets of neurons that die by apoptosis shortly after the emergence of the adult from the pupal case at the conclusion of metamorphosis, in a low steroid hormone environment. Both sets of neurons accumulate reaper and grim transcripts, but not hid transcripts immediately prior to their death. Application of the biologically active steroid 20-hydroxyecdysone prevents transcription of these genes and prevents the death of these neurons. We have identified a genomic region that regulates expression of the grim gene that is sensitive to the titer of 20E. We are currently characterizing this region to determine the mechanism by which 20E represses transcription of this gene.
The steroid hormone 20E drives Drosophila development by interacting with nuclear receptors that act as ligand regulated transcription factors. To define the cellular mechanisms and interactions involved in nuclear receptor signaling, we are currently conducting a screen to identify genes that are involved in nuclear receptor signaling pathways. This screen is designed to identify genes that function during metamorphosis when the animal undergoes a dramatic reorganization. Characterization of genes identified in this screen will help define the molecular pathways that are regulated by hormones during development.
Schubiger, M., S. Tomita, C. Sung, S. Robinow, and J. W. Truman (2003). Isoform specific control of gene activity in vivo by the Drosophila ecdysone receptor. Mech. Dev. (in press).
Suster, M. L., J.-R. Martin, C. Sung, and S. Robinow (2003). Targeted expression of tetanus toxin reveals sets of neurons required for larval locomotion in Drosophila. J. Neurobiology 55:233-246.
Lee T, Marticke S, Sung C, Robinow S, Luo L. 2000. Cell autonomous requirement fo the USP/EcR-B ecdysone receptor for mushroom body neuronal remodeling. Neuron 28:807-818.
Sung C, Robinow S. 2000. Character-ization of the regulatory elements controlling neuronal expression of the A-isoform of the ecdysone receptor gene of Drosophila melano-gaster. Mech Devel 91:237-248.
Draizen TA, Ewer J, Robinow S. 1999. Genetic and hormonal regulation of the death of peptidergic neurons in the Drosophila CNS. J Neurobiol 38:455-465.
Robinow S, Draizen TA, Truman JW. 1997. Genes that induce apoptosis: transcriptional regulation in identi-fied, doomed neurons of the Droso-phila CNS. Devel Biol 190:206-213.