NTUIMCB_Eng

Recent Research Topics

Programmed cell death and cell migration in C. elegan

Laboratory: Molecular developmental Genetics

Our lab is interested in two aspects of development, programmed cell death and cell migration. We study these processes in the model organism C. elegans. 

Removal of apoptotic cells during programmed cell death 

Cell migration 

Programmed cell death (apoptosis) is important for the development and homeostasis of metazoans. Cells die by programmed cell death are removed by the engulfment process. The engulfment process not only passively removes apoptotic cells but also actively promotes cell death. During the development of a C. elegans adult hermaphrodite131 somatic cells undergo programmed cell death. These cells die at specific times and in specific locations, which are essentially invariable from animal to animal. These features make C. elegans a great model organism to study the engulfment of apoptotic cells. We have undertaken genetic, molecular and biochemical approaches to study the mechanism of cell-corpse engulfment in C. elegans. Our work has identified a signaling molecule CED-12 and showed that it interacts with DOCK180-like CED-5 protein to activate Rac GTPase CED-10 in an engulfing cell (Dev. Cell, 2001). We also showed that PSR-1 likely acts as a cell-surface receptor to transduce the eat-me signal of apoptotic cell, likely through the direct interaction of its intracellular domain with signaling molecules CED-5 and CED-12 in an engulfing cell (Science, 2003).

Selected Research Publications

A. REFEREED PAPERS:

I. Cell Migration and Cell Death

1.       Wu, Y.C. and Horvitz, H.R. C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180. Nature, 392, 501-504 (1998).

2.       Wu, Y.C. and Horvitz, H.R. The C. elegans cell corpse engulfment gene ced-7 encodes a protein similar to ABC transporters. Cell, 93, 951-960 (1998).

3.       Wu, Y.C., Stanfield, G.M. and Horvitz, H.R. NUC-1, a Caenorhabditis elegans DNase II homolog, functions in an intermediate step of DNA degradation during apoptosis. Genes & Dev., 14, 536-548 (2000).

4.       Ledwich, D., Wu, Y.C. , Driscoll, M. and Xue, D., Analysis of programmed cell death in the nematode Caenorhabditis elegans. Methods in Enzymology , 322, 76-88(2000).

5.       Wu, Y.C. *, Tsai, M.C., Cheng L.C., Chou, C.C. and Weng N.Y., C. elegans CED-12 acts in the conserved CrkII/DOCK180/Rac pathway to control cell migration and cell-corpse engulfment. Dev. Cell, 1, 491-502 (2001). *corresponding author [This paper was the subject of a Preview by Barbara Conradt on Cell Engulfment, No Sooner ced Than Done, Dev. Cell 1, 1-20 (2001)]

6.       Wu, Y.C. *, Cheng, T.W., Lee, M.C. and Weng, N.Y. Distinct Rac activation pathways control C. elegans cell migration and axon outgrowth. Dev. Biol., 250, 145-155 (2002). * corresponding author

7.       Wang, X. # , Wu, Y.C. # *, Fadok, V., Lee, M., Gengyo-Ando, K., Cheng, L., Ledwich, D., Hsu, P., Chen, J., Chou, B., Henson, P., Mitani, S. and Xue, D.* Cell Corpse Engulfment Mediated by C. elegans Phosphatidylserine Receptor Through CED-5 and CED-12. Science 302,1563-1566 (2003) #These authors contributed equally to this work. * corresponding author [This paper was the subject of a Perspective by John Savil, Chris Gregory and Chris Haslet on Eat Me or Die, Science 302, 1516-1527 (2003)]

8.       deBakker, C.D., Haney, L.B., Kinchen, J. M., Grimsley, C., Lu,M., Klingele, D., Hsu, P.K., Chou, B.K., Cheng, L.C., Blangy, A., Sondek, J., Hengartner, M.O., Wu, Y.C. and Ravichandran, K.S. Phagocytosis of apoptotic cells is regulated by a UNC-73/TRIO ─ MIG-2/RhoG signaling module and Armadillo repeats of CED-12/ELMO. Curr. Biol. 14, 2208-2216(2004) [ This paper was the subject of a Dispatch by Peter Henson on Engulfment: Ingestion and Migration with Rac, Rho and TRIO, Curr. Biol., R29-30 (2004) ]

9.       Liu, W.H., Lin, Y.L., Wang, J.P., Liou, W., Hou, R.F., Wu, Y.C.* and Liao, C.L.* Restriction of Vaccinia Virus Replication by a ced-3 and ced-4 -Dependent Pathway in C. elegans. Proc. Natl. Acad. Sci. USA. 103, 4174-4179 (2006). *corresponding authors [ This paper was the subject of a Commentary by Shai Shaham on Worming into the cell: viral reproduction in Caenorhabditis elegans, PNAS (2006) 103, 3955–3956 ]

10.    Chen, K.Y., Pan, H., Lin, M.J., Li, Y.Y., Wang, L.C., Wu, Y.C., Hsiao, K.M. Length-dependent toxicity of untranslated CUG repeats on Caenorhabditis elegans. Biochem. Biophys. Res. Commun. 352, 774-977 (2007).

11.    Wang, L.C., Hung, W.T., Pan H., Chen, K.Y., Wu, Y.C., Liu Y.F., Hsiao K.M., Growth-dependent effect of muscleblind knockdown on Caenorhabditis elegans. Biochem. Biophys. Res. Commun. 366, 705-709 (2008).

12.    Lin, Y.M., Chen, Y.R., Lin, J.R., Wang, W.J., Inoko A., Inagaki, M., Wu, Y.C. , Chen R.H., eIF3k regulates apoptosis in epithelial cells by releasing caspase 3 from keratin-containing inclusions. J. Cell Sci. 121:2382-2393 (2008).

13.    Tong, A., Lynn, G., Ngo, V, Wong, D., Moseley, S.L., Ewbank J.J., Goncharov, A., Wu, Y.C., Pujol, N., and Chisholm, A.D., Negative regulation of Caenorhabditis elegans epidermal damage responses by death-associated protein kinase. Proc. Natl. Acad. Sci. USA. 106:1457-1461 (2009).

14.    Yeh, C.H., Yang, H. J., Lee, I. J. and Wu, Y.C.* C. elegans TLK-1 controls cytokinesis by localizing AIR-2/Aurora B to midzone microtubules. Biochem. Biophys. Res. Commun. 400, 187-193 (2010). * corresponding author

15.    Hsu, T. and Wu, Y.C.* Engulfment of apoptotic cells in C. elegans is mediated by integrin alpha/SRC signaling, Curr. Biol. 20:477-486 (2010). *corresponding author [ This paper was the subject of a Dispatch by Veera D'mello and Raymond B. Birge on Apoptosis: conserved roles for integrins in clearance, Current Biology (2010) 20, R324-327 ]

16.    Huang, C.Y., Chen, J.Y., Wu, S.C., Tan, C.H., Tzeng, R.Y., Lu, P.J., Wu, Y.F., Chen, R.H.*, Wu, Y.C.* C. elegans EIF-3.K Promotes Programmed Cell Death through CED-3 Caspase PLoS ONE, 7, e336584 (2012). * corresponding authors

17.    Hsieh, H.H. # , Hsu, T.-Y. # , Jiang, H.S. Wu, Y.C.* Integrin a PAT-2/CDC-42 Signaling Is Required for Muscle-Mediated Clearance of Apoptotic Cells in Caenorhabditis elegans. PLoS Genet. 8(5): e1002663. (2012). # These authors contributed equally to this work. * corresponding author

18.    Wu, Y.C., Wang, X, Xue, D. Methods for studying programmed cell death in C. elegans. Methods Cell Biol. 107:295-320. Review (2012).

19.    Jiang, H.S. and Wu, Y.C.* LIN-3/EGF promotes the programmed cell death of specific cells in Caenorhabditis elegans by transcriptional activation of the pro-apoptotic gene egl-1. PLoS Genet. 10(8):e1004513 (2014). * corresponding author

20.    Huang, T.F., Cho, C.Y., Cheng, Y.T., Huang, J.W., Wu, Y.Z., Yeh, A.Y., Nishiwaki, K., Chang, S.C., Wu, Y.C.* BLMP-1/Blimp-1 regulates the spatiotemporal cell migration pattern in C. elegans. PLoS Genet. 10(6):e1004428 (2014). * corresponding author

21.    Lin, Y.H., Chen, Y.C., Kao, T.Y., Lin, Y.C., Hsu, T.E., Wu, Y.C., Ja, W.W., Brummel, T.J., Kapahi, P., Yuh, C.H., Yu, L.K., Lin, Z.H., You, R.J., Jhong, Y.T., Wang, H.D. Diacylglycerol lipase regulates lifespan and oxidative stress response by inversely modulating TOR signaling in Drosophila and C. elegans. Aging Cell. 13(4):755-764 (2014).

22.    Chepyala, S.R., Chen, Y.C., Yan, C.C., Lu, C.Y., Wu, Y.C.* and Hsu, C.P.* Noise propagation with interlinked feed-forward pathways. Sci. Rep. 6:23607. doi: 10.1038/srep23607 (2016). *corresponding authors

23.    Conradt B, Wu YC*, Xue D. Programmed Cell Death During Caenorhabditis elegans Development. Genetics. 2016 Aug;203(4):1533-62. doi: 10.1534/genetics.115.186247.

24.    Yeh HY, Lin SW, Wu YC, Chan NL, Chi P. Functional characterization of the meiosis-specific DNA double-strand break inducing factor SPO-11 from C. elegans. Sci. Rep. 2017 May 24;7(1):2370. doi: 10.1038/s41598-017-02641-z.

25.    Chiu H, Zou Y, Suzuki N, Hsieh YW, Chuang CF, Wu YC, Chang C. Engulfing cells promote neuronal regeneration and remove neuronal debris through distinct biochemical functions of CED-1. Nat Commun. 2018 Nov 19;9(1):4842. doi: 10.1038/s41467-018-07291-x.

II. Application of Nanomaterials in Biology

1.       Lin, C.C.*, Yeh, Y.C., Yang, C.Y, Chen, C.L., Chen, G.F., Chen, C.C.*, Wu, Y.C.* Selective binding of mannose encapsulated gold nanoparticles to type 1 pili in Escherichia coli. J. Am. Chem. Soc., 124, 3508-3509 (2002). * corresponding authors

2.       Lin, C.C., Yeh, Y.C., Chen, G., Yang, C., Chen, Y., Wu, Y.C. and Chen, C.C. Quantitative Analysis of Multivalent Interactions of Carbohydrate Encapsulated Gold Nanoparticles with Concanavalin Chem. Com. 23, 2920-2921 (2003).

3.       Chen, C. C.,* Liu, Y.C., Wu, C.H., Yeh, C.C., Su, M.T. and Wu, Y.C.* Preparation of Fluorescent Silica Nanotubes and their Application in Gene Delivery. Adv. Mater . 17, 404-407 (2005) *corresponding author

4.       Chen,C.C., * Lin,I.P., Tzeng, S.C., Wang, J.W., Wu, C.H., Chen, Y.C., Chen, J.P., Chen, K.H., Su, M.T. and Wu, Y.C. * DNA-Gold Nanorod Conjugates for Remote Control of Localized Gene Expression by Near Infrared Irradiation. J. Am. Chem. Soc. 128, 3709-3715 (2006). *corresponding author

5.       Mohan, N., Chen, C.S., Hsieh, H.H., Wu, Y.C.* and Chang, H.C.* In vivo imaging and toxicity assessments of fluorescent nanodiamonds in Caenorhabditis elegans. Nano Lett. 10:3692-3699 (2010) *corresponding author [ This paper was the subject of Discovery news and PhysOrg.com. 

http://news.discovery.com/tech/nano-diamonds-diagnose-swallow.html 

http://www.physorg.com/news203230792.html ]

6.       Liu, Y. H., Tsai, Y. Y. 1, Chien, H. J., Chen. C. Y., Huang, Y. F., Chen, J. S., Wu, Y.C.* and Chen, C. C.* Quantum-dot-embedded silica nanotubes as nanoprobes for simple and sensitive DNA detection. Nanotechnology 22:155102-155107 (2011). *corresponding authors

7.       Kuo, Y., Hsu, T.Y., Wu, Y.C. *, Chang, H.C.* Fluorescent nanodiamond as a probe for the intercellular transport of proteins in vivo. Biomaterials 34(33):8352-8360 (2013). *corresponding authors

8.       Li, C.H., Kuo, T.R., Su, H.J., Lai, W.Y. , Yang, P.C., Chen, J.S. , Wang, D.Y. , Wu, Y.C.* and Chen, C.C.* Fluorescence-Guided Probes of Aptamer-Targeted Gold Nanoparticles with Computed Tomography Imaging Accesses for in Vivo Tumor Resection. Sci. Rep., 5:15675 | DOI: 10.1038/srep15675 (2015) *corresponding authors 

B. BOOKS AND BOOK CHAPTERS 

1.    Xue, D., Wu, Y.C., and Shah, M.M. (2002) Programmed cell death in C. elegans : the genetic framework. Apoptosis. The Molecular biology of Programmed Cell Death: Frontiers in Molecular Biology, M. Jacobson and N. McCarthy, ed. Oxford University Press. 

2.    Wu, Y.C., and Xue, D. (2003) Programmed cell death in C. elegans . Essentials of apoptosis: Guide for Basic and Clinical Research. The Humanna Press Inc. 

3.    Wu, Y.C., Wang, X. and Xue, D. Methods for Studying Programmed Cell Death in C. elegans . CAENORHABDITIS ELEGANS : CELL BIOLOGY AND PHYSIOLOGY, SECOND EDITION, J. Rothman and A. Singson, ed. Academic Press. 107, 297-320 (2012).

Courses information

C. elegans core facility service

http://cecore.life.nthu.edu.tw/