Understanding how cells move and how they make and break adhesions to change the shape of animal embryos has broad implications for our knowledge of how birth defects occur, and has provided important insights into the mechanisms that lead to cancer. Using the powerful genetics and genomics tools available in the C. elegans model system, our work focuses on the genetic basis of morphogenesis in the epidermis of the early C. elegans embryo. We study three events: (1) Dorsal intercalation: epidermal cells intercalate to form a single row of cells, much like cells in early human embryos, a process that involves non-muscle myosins and changes in cell adhesion; (2) Ventral enclosure: ventral epidermal cells migrate and meet at the ventral midline to cover the embryo in epidermis, an event that shares similarities with closing of wounds and other embryonic events in humans; and (3) Embryonic elongation: Cadherin-dependent anchoring of the actin cytoskeleton is crucial for a coordinated changes of shape of epidermal as the embryo elongates. We use sophisticated live cell imaging in living embryos to study specific cell behaviors in dorsal and ventral cells, and the molecular pathways that control them. The projects in our laboratory are aimed at characterizing the molecular pathways that allow these cell migrations to occur.
Zoology 470 - Introduction to Animal Development (every spring)
Biocore 303 - Cellular Biology (every spring)
Note to prospective graduate students:
Our laboratory seeks motivated students who are interested in the interface between cell and developmental biology. Training opportunities in our laboratory include: forward genetic screening, reverse genetics, RNA-mediated interference, production of transgenic animals "4-dimensional" microscopy. We use the nematode, C. elegans, as our primary model system to understand the cellular and molecular basis of morphogenesis, i.e., how embryos change their shape during early development. Along with outstanding research opportunities, we also highly encourage development of a strong teaching and outreach portfolio for future career success.
Graduate students currently supervised:
Tim Loveless (firstname.lastname@example.org)
Cellular and Molecular Biology PhD student
Elise Walck-Shannon (email@example.com)
Genetics PhD student
Bethany Lucas (firstname.lastname@example.org)
Genetics PhD student
Xianqiang Shao (email@example.com)
Genetics PhD student
Postdoctoral fellows current supervised:
- Allison Lynch (firstname.lastname@example.org)
Students supervised who have recently earned graduate degrees:
Blake Martin (Biophysics Ph.D)
Allison Lynch (Genetics, Ph.D.)
Role of MAGI-1 during C. elegans morphogenesis
Stephanie Maiden (Molecular and Cellular Pharmacology, Ph.D.)
Molecular analysis of alpha-catenin function in C. elegans
Ryan King (Cellular and Molecular Biology, Ph.D.)
Molecular regulation of cell rearrangement in the dorsal epidermis of C. elegans
Chris Lockwood (Genetics, Ph.D.)
Structure and function of the Discs large homology, DLG-1, in C. elegans.
Tina Tuskey Lockwood (Cellular and Molecular Biology, Ph.D.)
Molecular analysis of the ZO-1 orthologue in C. elegans
Tim Walston (Genetics, Ph.D.).
Multiple Roles for Dishevelleds during Morphogenesis in the C. elegans embryo.
Mark Sheffield (Genetics, Ph.D.).
The role of UNC-34/Enabled during Morphogenesis in the C. elegans embryo.
Publications (for a complete list, please go here)
- Maiden, S.L., Harrison, N., Keegan, J., Cain, B., Lynch, A.M., Pettitt, J., and Hardin, J. (2013). Specific conserved C-terminal amino acids of Caenorhabditis elegans HMP-1/a-catenin modulate F-actin binding independently of vinculin. J. Biol. Chem. 288:5694-706.
- Hardin, J., Lynch, A., Loveless, T., and Pettitt, J. (2013). Cadherins and their partners in the nematode worm Caenorhabditis elegans. In "The Molecular biology of Cadherins" (ed. F. van Roy). Elsevier, in press.
- Hardin, J. (2011). Imaging embryonic morphogenesis in C. elegans. In: Joel H. Rothman and Andrew Singson, editors: Methods In Cell Biology, Vol 106, Oxford: Academic Press; 2011, p. 377-412.
- Walston, T. and Hardin, J. (2011). Visualizing cell contacts and cell polarity in Caehorhabditis elegans embryos. In "Imaging in Developmental Biology: A Laboratory Manual" (Sharpe, J., Wong, R.O., eds). Cold Spring Harbor: Cold Spring Harbor Press, pp. 229-244.
Hardin, J. (2006). Confocal and Multi-Photon Imaging of Living
Embryos. In Handbook of Biological Confocal Microscopy,
3e (J. Pawley, ed.). New York: Plenum, pp. 746-768.
Sims, P., Albrecht, R., Pawley, J.B., Centonze, V., Deerink,
T., and Hardin, J. (2006). When Light Microscope Resolution
Is Not Enough: Correlational Light Microscope and Electron
Microscope. In Handbook of Biological Confocal Microscopy,
Chisholm, A. and Hardin, J. (2005). Epidermal morphogenesis.
In WormBook, ed. The C. elegans Research
Selected papers in refereed national/international journals:
- Lynch, A.M., Grana, T., Cox-Paulson, E., Couthier, A., Cameron, M., Chin-Sang, I., Pettitt, J., and Hardin, J. (2012). A genome-wide functional screen identifies MAGI-1 as an L1CAM-dependent stabilizer of apical junctions in C. elegans. Curr. Biol., in press.
- Loveless, T. and Hardin, J. (2012). Cadherin complexity: recent insights into cadherin superfamily function in C. elegans. Curr. Opin. Cell Biol. 24, in press. DOI: 10.1016/j.ceb.2012.06.008
- Cox-Paulson, E., Walck-Shannon, E., Lynch, A., Yamashiro, S., Zaidel-Bar, R., Celeste C. Eno, C., Ono, S., and Hardin, J. (2012). Tropomodulin protects a-catenin-dependent junctional actin networks under stress during epithelial morphogenesis. Curr. Biol. 22:1500-1505.
- Ikegami, R., Simokat, K., Zheng, H., Dixon, L., Garriga, G., Hardin, J. and Culotti, J. (2012). Semaphorin and Eph receptor signaling guide a series of cell movements for ventral enclosure in C. elegans. Curr. Biol. 22:1–11.
- Maiden, S.L. and Hardin, J. (2011). The secret life of a-catenin: moonlighting during morphogenesis. J. Cell Biol. 195:543–552.
- Neukomm, L.J., Frei, A.P., Cabello, J., Kinchen, J.M., Zaidel-Bar, R., Ma, Z., Haney, L.B., Hardin, J., Ravichandran, K.S., Moreno, S., and Hengartner, M.O. (2011). Loss of the RhoGAP SRGP1 promotes the clearance of dead and injured cells in Caenorhabditis elegans. Nature Cell Biol. 13:79-86.
- Zaidel-Bar, R., Joyce, M.J., Lynch, A.M., Witte, K., Audhya, A., and Hardin, J. (2010). The F-BAR domain of SRGP-1 facilitates cell-cell adhesion during C. elegans morphogenesis. J. Cell Biol. 191, 761-9.
- Kwiatkowski, A.V., Maiden, S.L., Pokutta, S., Choi, H.-J., Benjamin, J.M., Lynch, A.M., Nelson, W.J., Weis, W.I., and Hardin, J. (2010). In vitro and in vivo reconstitution of the cadherin-catenin-actin complex from Caenorhabditis elegans. PNAS 107:14591-14596.
- Grana, T.M., Cox, E.A., Lynch, A.M., and Hardin, J. (2010). SAX-7/L1CAM and HMR-1/cadherin function redundantly in blastomere compaction and non-muscle myosin accumulation. Dev. Biol. 344:731–744.
- King, R.S., Maiden, S.L., Hawkins, N.C., Kidd, A.R., Kimble, J., Hardin, J., and Walston, T.D.(2009). POP-1 asymmetry and morphogenesis defects in dsh-2 mutant embryos can be rescued by either the DIX or DEP domain of DSH-2. Dev. Biol. 328: 234-44.
- Thomas-Virnig, C.L., Sims, P.A., Simske, J.S., and Hardin, J. (2005) The inositol 1,4,5-trisphosphate receptor regulates epidermal cell migration in Caenorhabditis elegans. Curr Biol. 14:1882-7.
- Cox, E.A. and Hardin, J. (2004) Sticky worms: adhesion complexes in C. elegans. J. Cell Sci. 117:1885-97.
- Cox, E.A., Tuskey, C. and Hardin, J. (2004) Cell adhesion receptors in C. elegans. J. Cell Sci. 117:1867-70.
- Walston, T., Tuskey, C., Edgar, L., Hawkins, N., Ellis, G., Bowerman, B., Wood, W., and Hardin, J. (2004). Multiple Wnt signaling pathways converge to orient the mitotic spindle in early C. elegans embryos. Dev Cell 7:831-41.
- Simske, J.S., Köppen, M., Sims, P.A., Hodgkin, J., and Hardin, J.D. (2003). The cell junction protein VAB-9 regulates adhesion and epidermal morphology in C. elegans. Nature Cell Biol. 5:619-625.
- Pettitt, J., Cox, E.A., Broadbent, I.D., Fleet, A. and Hardin, J. (2003) The C. elegans p120 catenin homologue, JAC-1, modulates cadherin-catenin function during epidermal morphogenesis. J. Cell Biol., 162:15-22.
- Koeppen, M., Simske, J.S., Sims, P.A., Firestein, B.L., Hall, D.H., Radice, A.D., Rongo, C. and Hardin, J.D. (2001) Cooperative regulation of AJM-1 controls junctional integrity in Caenorhabditis elegans epithelia. Nature Cell Biol. 3:983-991.