Chiou-Fen Chuang, PhD

Lab office: 4068 MBRB

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.

(Complete list of publications on Google Scholar)

1. Siete C. ^†, Xiong, R. ^†, Khalid, A.*, and Chuang, C.-F. (2024). Immobilization of C. elegans with different concentrations of an anesthetic for time-lase imaging of dynamic protein trafficking in neurons. microPublication Biology. 10.17912/micropub.biology.001069. ^†These authors contributed equally to this work. *UIC undergraduate student.
2. Xiong, R.*, Hsieh, Y.-W. ^*, and Chuang, C.-F. (2022). CEPsh glia development is not required for general AWC identity or AWC asymmetry. microPublication Biology. 10.17912/micropub.biology.000636.  ^†These authors contributed equally to this work.
3. Xiong, R., Hsieh, Y.-W., and Chuang, C.-F. (2022). mNG-tagged mls-2 knock-in alleles in C. elegans. microPublication Biology. 10.17912/micropub.biology.000529.
4. Hsieh, Y.-W. and Chuang, C.-F. (2022). Analysis of unc-62 expression pattern in C. elegans embryonic AWC neurons. microPublication Biology. 10.17912/micropub.biology.000530.
5. Hsieh, Y.-W.*, Xiong, R.*, and Chuang, C.-F. (2021). Synergistic roles of homeodomain proteins UNC-62 homothorax and MLS-2 HMX/NKX in the specification of olfactory neurons in Caenorhabditis elegans. Genetics 219(2). doi: 10.1093/genetics/iyab133. ^*These authors contributed equally to this work.
6. Alqadah, A., Hsieh, Y.-W., Xiong, R., Lesch, B.J., Chang, C., and Chuang, C.-F. (2019). A universal transportin protein diversifies olfactory neurons via specific nuclear import of a sox-2-activating factor. Proceedings of the National Academy of Sciences of the United States of America. 116, 25137-25146.
7. Chiu, H., Zou, Y., Suzuki, N., Hsieh, Y.-W., Chuang, C.-F., Wu, Y.-C., and Chang, C. (2018). Engulfing cells promote neuronal regeneration and remove neuronal debris through distinct biochemical functions of CED-1. Nature Communications 9. doi: 10.1038/s41467-018-07291-x.
8. Alqadah, A., Hsieh, Y.-W., Morrissey, Z., and Chuang, C.-F. (2018). Asymmetric development of the nervous system. Invited review for the special issue on development, disease and repair of the nervous system. Developmental Dynamics. doi: 10.1002/dvdy.24595.
9. Hsieh, Y.-W., Alqadah, A., and Chuang, C.-F. (2017). Mechanisms controlling diversification of olfactory sensory neuron classes. Invited review for Cellular and Molecular Life Sciences. doi:10.1007/s00018-017-2512-2.
10. Oh, K.H., Haney, J.J., Wang, X., Chuang, C.-F., Richmond, J.E., and Kim, H. (2017). ERG-28 controls BK channel trafficking in the ER to regulate synaptic function and alcohol response in C. elegans. eLife 2017;6:e24733. doi:http://dx.doi.org/10.7554/eLife.24733
11. Hsieh, Y.-W., Alqadah, A., and Chuang, C.-F. (2016). An optimized protocol for electrophoretic mobility shift assay using infrared fluorescent dye-labeled oligonucleotides. Journal of Visualized Experiments 117: e54863. doi:10.3791/54863
12. Alqadah, A., Hsieh, Y.-W., Xiong, R., and Chuang, C.-F. (2016). Stochastic left-right neural asymmetry in C. elegans.  Invited review for the special issue on left-right asymmetries of pattern formation: integrating chiral information from cells to organisms. Philosophical Transactions of the Royal Society B 372: 20150407. doi: 10.1098/rstb.2015.0407.
13. Alqadah, A., Hsieh, Y.-W., and Chuang, C.-F. (2016). Sox2 goes beyond stem cell biology. Cell Cycle 15, 777-778, doi: 10.1080/15384101.2015.1137714.
14. Alqadah, A., Hsieh, Y.-W., Schumacher, J.A., Wang, X., Merrill, S.A., Millington, G., Bayne, B*., Jorgensen, E.M., and Chuang, C.-F. (2016). SLO potassium channels couple gap junctions to inhibition of calcium signaling in olfactory neuron diversification. *Undergraduate student. PLoS Genetics 12(1): e1005654. doi:10.1371/journal.pgen.1005654.
15. 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.
16. 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.
17. 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.
18. Alqadah, A., Hsieh, Y.-W., and Chuang, C.-F. (2014). A molecular link between distinct neuronal asymmetries. Cell Cycle, doi: 10.4161/cc.29010.
19. 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.
20. 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.
21. Zou, Y., Chiu, H., Zinovyeva, A., Ambros, V., Chuang, C.-F.*, and Chang, C*. (2013). Developmental decline in neuronal regeneration by the progressive change of two intrinsic timers in C. elegans. *Senior authors contributed equally. Science 340, 372-376.
22. Zou, Y., Chiu, H., Domenger, D., Chuang, C.-F.*, and Chang, C*. (2012). The lin-4 microRNA targets the LIN-14 transcription factor to inhibit netrin-mediated axon attraction. *Senior authors contributed equally. Science Signaling 5, research article ra43
23. Lobikin, M., Wang, G., Xu, J., Hsieh, Y.-W., Chuang, C.-F., Lemire, J.M., and Levin, M. (2012). Early, nonciliary role for microtubule proteins in left-right patterning is conserved across kingdoms. Proc. Natl. Acad. Sci. 109, 12586-91.
24. 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
25. 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.
26. Chiu, H., Alqadah, A., Chuang, C.-F., and Chang, C (2011). C. elegans as a genetic model to identify novel cellular and molecular mechanisms underlying nervous system regeneration. Cell Adhesion & Migration 5, 387-394.
27. 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.
28. 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.
29. Gabel, C. V., Antonie, F., Chuang, C.-F., Samuel, A. D., and Chang, C. (2008). Distinct cellular and molecular mechanisms mediate initial axon development and adult-stage axon regeneration in C. elegans.  Development 135, 1129-1136
30. 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.
31. 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.

PhD, California Institute of Technology, Pasadena, CA

MS, National Yang-Ming University, Taipei, Taiwan