Research Interests

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 two events: (1) Dorsal epidermal cells intercalate to form a single row of cells, much like cells in early human embryos, and process that involves Wnt signaling and other polarizing events; and (2) Ventral epidermal cells migrate and meet at the ventral midline to cover the embryo in epidermis, and event that shares similarities with closing of wounds and other embryonic events in humans. 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.

Courses:

Zoology 470 - Introduction to Animal Development
Biocore 303 - Cellular Biology
Biocore 301 - Evolution, Ecology, & Genetics

Jeff Hardin's Course Page (Zoology 470 & Biocore)
Dynamics of Development Tutorial

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" and multiphoton excitation 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.

Graduate students currently supervised:

Ryan King (CMB) (rsking@students.wisc.edu)
    Molecular regulation of cell rearrangement in C. elegans

Allison Lynch (amlynch2@wisc.edu)
    Genetic analysis of ?-catenin in C. elegans

Stephanie Maiden (maiden@wisc.edu)
    Genetic analysis of cell migration in C. elegans

Tim Loveless (tloveless@wisc.edu)
    Molecular Biocsciences PhD student

Students supervised who've recently earned graduate degrees:

Chris Lockwood (Genetics, Ph.D.)
    Molecular regulation of epithelial junctions in C. elegans.

Tina Tuskey (CMB, 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.

Mathias Koeppen
    Role of the protein AJM-1 in epithelial junction assembly in C. elegans.

Christina Thomas-Virnig
    Role of the inositol triphosphate receptor, ITR-1, during morphogenesis in C. elegans.

Kristin Simokat
    The role of Eph and semaphorin guidance molecules during C. elegans epithelial morphogenesis.

Selected Publications

Books/Monographs:

• 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, pp. 846-860.

• Chisholm, A. and Hardin, J. (2005). Epidermal morphogenesis. In WormBook, ed. The C. elegans Research Community, http://www.wormbook.org
  

Papers in refereed national/international journals:

Walston, T. D. and Hardin, J. (2006). Wnt-dependent spindle polarization in the early C. elegans embryo. Semin Cell Dev Biol 17, 204-13.

Walston, T., Guo, C., Proenca, R., Wu, M., Herman, M., Hardin, J., and Hedgecock, E. (2006). mig-5/Dsh controls cell fate determination and cell migration in C. elegans. Dev Biol 298, 485-97.

Lee, J. Y., Marston, D. J., Walston, T., Hardin, J., Halberstadt, A., and Goldstein, B. (2006). Wnt/Frizzled signaling controls C. elegans gastrulation by activating actomyosin contractility. Curr Biol 16, 1986-97.

Hardin, J., and Illingworth, C. A. (2006). A homologue of snail is expressed transiently in subsets of mesenchyme cells in the sea urchin embryo and is down-regulated in axis-deficient embryos. Dev Dyn 235, 3121-31.

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.

Sims, P.A., Lockwood, C.A., and Hardin, J (2005). Integrating light and TEM information with F-TEM images. Micr. Today 13(5), 16-18.

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.

Hardin, J. and Walston, T. (2004). Models of morphogenesis: the mechanisms and mechanics of cell rearrangement. Curr. Opin. Genetics & Dev. 14, 399-406.

Hardin, J. and Lockwood, C. (2004) Skin tight: cell adhesion in the epidermis of Caenorhabditis elegans. Curr. Opin. in Cell Biol. 16:486-492.

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 funciton during epidermal morphogenesis. J. Cell Biol., 162:15-22.

Simske, J.S., and Hardin, J.  (2001)  Getting into shape: epidermal morphogenesis in Caenorhabditis elegans embryos.  Bioessays, 23: 12-23.

Heid, P.J., Raich, W.B., Smith, R., Mohler, W.A., Gendreau, S.B., Rothman, J.H., and Hardin, J. (2001). The zinc finger protein DIE-1 is required for late events during epithelial cell rearrangement in C. elegans. Dev. Biol. 236:165-180.

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.