Welcome to the Hardin Lab! 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. To find out more, click here...
Our work is supported by the National Institute of General Medical Sciences, NIH.
Interested in a postdoctoral position? Click here for more information...
Recent NewsDecember 2015
F1000 review of the cadherin/catenin complex in C. elegans. F1000 Reviews.
Proteomic analysis of the cadherin/catenin complex in C. elegans (collaboration with Jon Audhys's group):
Callaci, S., Morrison, K., Shao, X., Schuh, A.L. Wang, Y., Yates III, J.R., Hardin, J., and Audhya, A. (2015). Phosphoregulation of the C. elegans cadherin-catenin complex. Biochemistry 472:339-52.. PubMed
hmp-1 mutant embryo rescued with a quadruple mutant phosphomimetic form of HMP-1 tagged with gfp (Xiangqiang Shao).
Dorsal intercalation in C. elegans uses a conserved Trio/CARMIL system upstream of Rac and RhoG. Development 142, 3549-3560. PubMed
crml-1(gm326) dorsal cells have excessive protrusive activity, which can be suppressed by GEF1 loss of function n unc-73(rh40) mutants. Left-hand cells are psuedocolored green. Yellow arrows denote excessive, lateral protrusions. Scale bar is 5 μm. [Elise Walck-Shannon]
Student news: Congratulations to Elise Walck-Shannon, who defended her thesis July 29, 2015!
A PDF of the flyer can be found here.
Blake Martin received a Gilliam fellowship from HHMI!
Angstroms to embryos: structure-function analysis of the cadherin complex in C. elegans
(collaboration with Bill Weis, Stanford, and Hee-Jung Choi, Seoul Nat. Univ.; Developmental Cell 33, 82–93)
Electrostatic representation of zebrafish β-catenin (left) and C. elegans HMP-2 (right). [Hee-Jung Choi, Bill Weis, Tim Loveless]
Minor updates to ImageJ plugins
are available. Go to the Microscopy page.
Cell rearrangement review
Walck-Shannon, E. and Hardin, J. (2014). Cell intercalation from top to bottom. Nature Rev. Mol. Cell. Bio 15:34-48. Pubmed
Mapping functionally important domains in the C terminus of α-catenin
Maiden, S.L., Harrison, N., Keegan, J., Cain, B., Lynch, A.M., Pettitt, J., and Hardin, J. Specific conserved C-terminal amino acids of Caenorhabditis elegans HMP-1/α-catenin modulate F-actin binding independently of vinculin. J. Biol. Chem. 288:5694-706. PubMed
Homology model of the C terminus o HMP-1/α-catenin, using the metavinculin VH3 domain crystal structure as a template. Residues mutated in hmp-1 alleles are shown as space-filled molecules labeled with the amino acid number. (A) and (B) Residues mutated in strong loss-of-function alleles. (C) Residues mutated in hmp-1(fe4) and intragenic suppressor alleles. [Stephanie Maiden]
MAGI-1, AFD-1/afadin, and the cadherin interactome during morphogenesis
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. PubMed
Top: Wild-type embryo expressing an actin reporter during ventral enclosure. Bottom: a magi-1(RNAi) embryo. Cells migrate ventrally, but migration is irregular and cells display excess protrusive activity at the ventral midline. [Allison Lynch]
Tropomodulin protects adherens junctions under stress during morphogenesis
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. PubMed
hmp-1/α-catenin and unc-94/tropomodulin synergistically regulate embryonic morphogenesis. Purple, F-actin (phalloidin staining); green, JAC-1/p120ctn::GFP. Left: a hmp-1(fe4) embryo at the 1.5-fold stage. Junctions are largely normal. Right: a hmp-1(fe4);unc-94(RNAi) embryo. Junctions between seam cells and ventral and dorsal epidermal cells have ripped apart [Abbi Cox-Paulson]
Cell migration during ventral enclosure
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. PubMed
Ventral view of the pocket region of an embryo expressing Pplx-2::gfp; anterior at top right. The ventral midline (dashed line) and relative positions of expressing identified P cells (circles, closed circles are P9/10) and plexin expressing cells on the surface of the open ventral pocket (colored squares) are indicated. [Kristin Simokat and Richard Ikegami]
Maiden, S.L. and Hardin, J. (2011). The secret life of α-catenin: moonlighting during morphogenesis. J. Cell Biol. 195:543–552. PubMed
Loss of the RhoGAP SRGP-1 promotes the clearance of dead and injured cells
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. PubMed
ced-6 larvae accumulate cell corpses due to engulfment defects (arrowheads, left).
Engulfment defects are suppressed in ced-6;srgp-1 double mutants (right). [Lukas Neukomm]
SRGP-1/srGAP regulates membrane protrusion during cell-cell adhesion
(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.) PubMed JCB In This Issue
November 15, 2010 cover!
Embryo expressing SRGP-1::GFP (green) stained for actin (purple).
The inset shows extensive induced tubulations. [Ronen Zaidel-Bar].
Intramolecular regulation of alpha-catenin's ability to bind actin
(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.)
embryo stained with phalloidin. [Stephanie Maiden].
Cadherins and L1CAMs during cell-cell adhesion and gastrulation
(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.)
Color adjusted image of a devitellinized hmr-1(RNAi);sax-7(eq1) C. elegans embryo. Blastomeres are loosely adherent and cell division orientations are abnormal. [Theresa Grana].
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