Research:
Our research addresses three questions: (i) what is the molecular basis of embryogenesis? (ii) how does an organism sense potentially harmful stimuli? (iii) what are the genes and circuits that regulate sleep and wakefulness? We mainly use zebrafish as a model system, because genetic and imaging approaches can be combined to study complex behaviors and developmental processes in a vertebrate. 1. Vertebrate embryogenesis The vertebrate body plan is set up during gastrulation, when a ball of undifferentiated, totipotent cells is transformed into an embryo. This process results in the formation of the three germ layers (ectoderm, mesoderm, and endoderm) and the three axes (anterior-posterior, dorsal-ventral and left-right). We wish to understand how signaling pathways, transcription factors, chromatin modifications and non-coding RNAs regulate this process. We are using genetic, biophysical and in vivo imaging approaches to determine how signals move through fields of cells and elicit concentration dependent effects. In parallel, we use biochemical and genetic approaches to determine how chromatin modifications and non-coding RNAs regulate early development. 2. Sensory neuron development and function Animals protect themselves by sensing potentially harmful thermal, mechanical or chemical stimuli. This process of nociception is mediated by specific sensory receptors and circuits. We analyze the development and function of trigeminal sensory neurons, the primary nociceptors in the vertebrate head. We are using genetic and imaging approaches to study the molecules that regulate neuronal interactions and morphologies. In addition, we have begun to use in vivo imaging approaches and serial EM reconstruction to determine how different stimuli are encoded in the trigeminal ganglion and hindbrain. 3. Sleep and wakefulness The genetic and cellular mechanisms that control sleep and wake states remain largely elusive. We have established zebrafish as a model system for sleep research. Zebrafish have the basic hallmarks of sleep-like behaviors. Sleeping fish require stronger stimuli than awake fish to initiate movement and sleep deprivation is followed by increased sleep. In addition, the zebrafish brain expresses peptides that have been implicated in human sleep disorders. We are using genetic and pharmacological screens to isolate sleep regulators and use electrophysiological and imaging approaches to dissect sleep circuits.
Selected Publications: Giraldez, A.J., Cinalli, R. Glasner, M.E., Enright, A., Baskerville, S., Bartel, D. and Schier, A.F. (2005). MicroRNAs regulate brain morphogenesis in zebrafish. Science 308, 833-838. Sagasti, A., Guido, M., Raible, D.R. and Schier, A.F. (2005). Repulsive interactions shape the morphologies and functional arrangement of zebrafish peripheral sensory arbors. Current Biology 15, 804-814. Ciruna, B., Jenny, A., Lee, D., Mlodzik, M. and Schier, A.F. (2006). Planar cell polarity signalling couples cell division and morphogenesis during neurulation. Nature 439, 220-224. Giraldez, A.J., Mishima, Y., Rihel, J., Grocock, R.J., Van Dongen, S., Inoue, K., Enright, A.J. and Schier, A.F. (2006). Zebrafish miR-430 promotes deadenylation and clearance of maternal mRNAs. Science 312, 75-79. Prober, D.A., Rihel, J., Onah, A.A., Sung, R.-J., and Schier, A.F. (2006). Hypocretin/Orexin Overexpression Induces An Insomnia-Like Phenotype in Zebrafish. Journal of Neuroscience 26, 13400-10. Schier A.F. (2007) The maternal-zygotic transition: death and birth of RNAs. Science. 316, 406-7. Bennett, J.T., Stickney, H.L., Choi, W.-Y., Ciruna, B., Talbot, W.S., and Schier, A.F. (2007) Maternal Nodal and Zebrafish Embryogenesis. Nature 450, E1-2. Choi, W.-Y., Giraldez, A.J. and Schier, A.F. (2007). Target Protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430. Science 318, 271-274. Prober, D.A., Zimmerman, S., Myers, B.R., McDermott Jr., B.M., Kim, S.-H., Caron, S., Rihel, J., Solnica-Krezel, L., Julius, D., Hudspeth, A.J., and Schier, A.F. (2008). Zebrafish TRPA1 Channels are Required for Chemosensation but not for Thermosensation or Mechanosensory Hair Cell Function. Journal of Neuroscience 28, 10102-10.
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