University of Wisconsin–Madison
College of Agriculture and Life Sciences | School of Medicine and Public Health

Jeff Hardin

Professor

jdhardin@wisc.edu

608-262-9634

Integrative Biology
Using C. elegans to study cell movement and adhesion during embryonic development

Address
327 Zoology Research
Education
Ph.D., University of California, Berkeley (1987), Postdoctoral Research: Duke University
Department
Integrative Biology
Research Interests
We use the C. elegans embryo as a model for investigating cell movement and cell adhesion during embryonic development; understanding how cells move, and how they make and break adhesions has important implications for understanding birth defects during human development and for understanding cancer progression.
Research Fields
Cell Biology, Development, C. elegans

Research Description:
Our laboratory focuses on two major questions: (1) How do sheets of cells change shape and move during early embryonic development and (2) What controls those movements? Providing answers to these questions will have important implications for understanding human birth defects and cancer, both of which involve misregulation of these processes. We study the embryonic epidermis of the nematode, C. elegans as a model system. The epidermis is very simple, and we can visualize cell movements within it at the level of single cells. We have performed genome-wide functional screens and isolated mutants using forward genetics that identify genes required for three events in the epidermis: (1) a movement known as convergent extension in dorsal cells; (2) epiboly, or spreading of the epidermis, mediated by the ventral cells; and (3) elongation of the embryo, which requires actomyosin-based forces in lateral cells. We use “4-dimensional” microscopy (collecting multiple focal planes at each time point under computer control), and imaging of proteins tagged with the green fluorescent protein (GFP) to analyze these mutations at single-cell resolution. One major focus currently is on the cadherin complex, and how it is required for cell-cell adhesion during development.


Representative Publications:
Search PubMed for more publications by Jeff Hardin

Choi, H.-J.*, Loveless, T.*, Lynch, A.M., Bang, I., Hardin, J+, and Weis, W.I.+. A conserved phosphorylation switch controls the interaction between cadherin and β-catenin In vitro and In vivo. Developmental Cell 33, 82–93. [*Co-first authors; +Co-senior authors]

Walck-Shannon, E. and Hardin, J. (2014). Cell intercalation from top to bottom. Nature Rev. Mol. Cell. Bio 15:34-48.

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/α-catenin modulate F-actin binding independently of vinculin. J. Biol. Chem. 288:5694-5706.

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. 22, 1891–1899.

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 α-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.

Loveless, T. and Hardin, J. (2012). Cadherin complexity: recent insights into cadherin superfamily function in C. elegans. Curr. Opin. Cell Biol. 24:695-701.

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.