Education: PhD, California Institute of Technology
Website: Dr. Chuang's Lab
Molecular and genetic mechanisms of sensory diversity in C. elegans The nervous system generates a tremendous diversity of cell types. The specification of right cell types at right positions is a fundamental step allowing neurons to form functional circuits and networks for information processing and mediating behaviors. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can efficiently differentiate into functional neurons using developmental principles. Therefore, understanding how neurons acquire their distinct identities will lead to the development of strategies for cell replacement therapy. However, the molecular mechanisms that generate neuronal diversification are only partly understood.
The goal of our research is to use C. elegans as a model system to elucidate genes and mechanisms that generate sensory diversity at molecular and neural circuit levels. C. elegans consists of just 302 neurons with reproducible functions, morphologies, and synaptic connections. We know the identities, positions, and lineages of all neurons, as well as the complete wiring diagram in the C. elegans nervous system. In addition, the transparency of C. elegans allows us to visualize cell fates at single cell resolution in live animals using fluorescent markers. Furthermore, we can use C. elegans behaviors such as moving, mating, attraction towards specific odors, or avoidance from particular odors to analyze specific functions of individual neurons. Studies in C. elegans have led to the discovery of many important biological mechanisms (such as programmed cell death, RNAi, miRNA, axon guidance pathways) that are conserved from worms to humans. Thus, what we learn from C. elegans is significantly relevant to human research of similar biological or psychological areas of interest.
Our research interests have been focused on molecular and genetic analysis of two mechanisms that we identified for generating sensory neuron diversity.
1. Stochastic left-right neuronal asymmetry in a gap junction-dependent cell network.
2. Genetic switches between alternative sensory neuron fates.
In addition to further characterization of these mechanisms, our future research program will also explore novel molecular mechanisms underlying cellular diversity in the sensory system. As the genes and developmental pathways we study are evolutionarily conserved, we believe that insights obtained from these studies will provide entry points for studies in more complex organisms. We aim to translate our work to studies of vertebrate systems through collaborations.
Representative Publications (Complete list of publications on Google Scholar)
Alqadah, A., Hsieh, Y.-W., Schumacher, J.A., Wang, X., Merrill, S.A., Millington, G., Bayne, B*., Jorgensen, E.M., and Chuang, C.-F. SLO potassium channels couple gap junctions to inhibition of calcium signaling in olfactory neuron diversification. *Undergraduate student. PLoS Genetics, in press.
Alqadah, A., Hsieh, Y.-W., Vidal, B., Chang, C., Hobert, O., and Chuang, C.-F. (2015). Postmitotic diversification of olfactory neuron types is mediated by differential activities of the HMG-box transcription factor SOX-2. EMBO Journal 34, 2574-2589.
Vidal, B., Santella, A, Bao, Z., Chuang, C-F., and Hobert, O. (2015). C. elegans SoxB genes are dispensable for embryonic neurogenesis but required for terminal differentiation of specific neuron types. Development 142, 2464-2477.
Cochella, L., Tursun, B., Hsieh, Y.-W., Chuang, C.-F.*, and Hobert, O.* (2014). Two distinct types of neuronal asymmetries are controlled by the Caenorhabditis elegans zinc finger transcription factor die-1. *Senior authors contributed equally. Genes & Development 28, 34-43.
Alqadah, A., Hsieh, Y.-W., and Chuang, C.-F. (2014). A molecular link between distinct neuronal asymmetries. Cell Cycle, doi: 10.4161/cc.29010. [Epub ahead of print].
Hsieh, Y.-W., Alqadah, A., and Chuang, C.-F. (2014). Asymmetric neural development in the Caenorhabditis elegans olfactory system. Invited review for the special issue on Left-right asymmetry: advances and enigmas. Genesis, doi: 10.1002/dvg.22744. [Epub ahead of print].
Alqadah A., Hsieh, Y.W., and Chuang, C.-F. (2013). microRNA function in left-right neuronal asymmetry: perspectives from C. elegans. Frontiers in Cellular Neuroscience 7:158. doi:10.3389/fncel.2013.00158.
Schumacher, J.A., Hsieh, Y.-W., Chen, S., Pirri, J.K., Alkema, M.J., Li, W.-H., Chang, C., and Chuang, C.-F. (2012). Intercellular calcium signaling in a gap junction-coupled cell network establishes asymmetric neuronal fates in C. elegans. Development 139, 4191-4201
Hsieh, Y.-W., Chang, C., and Chuang, C.-F. (2012). The microRNA mir-71 inhibits calcium signaling by targeting the TIR-1/Sarm1 adaptor protein to control stochastic L/R neuronal asymmetry in C. elegans. PLoS Genetics 8, e1002864.
Chang, C., Hsieh, Y.-W., Bluma, J.L., Bargmann, C.I., and Chuang, C.-F. (2011). Microtubule-based localization of a synaptic calcium signaling complex specifies left-right neuronal asymmetry in C. elegans. Development 138, 3509-3518.
Taylor, R., Hsieh, Y.-W.., Gamse, J., and Chuang, C.-F. (2010). Making a difference together: reciprocal interactions in C. elegans and zebrafish asymmetric neural development. Development 137, 681-691.
Chuang, C.-F., VanHoven, M. K., Fetter, R. D., Verselis, V. K., and Bargmann, C. I. (2007). An innexin-dependent cell network establishes left-right neuronal asymmetry in C. elegans. Cell 129, 787-799.
Chuang, C.-F. and Bargmann, C. I. (2005). A Toll-interleukin 1 repeat protein at the synapse specifies asymmetric odorant receptor expression via ASK1 MAPKKK signaling. Genes & Development 19, 270-281.
Office: 4068 MBRB, MC 567