MECHANISMS of MORPHOGENESIS

Images in the banner (from left to right and top to bottom): DLG-1/Discs large::GFP during dorsal intercalation [M. Köppen]; Pdlg-1::GFP during ventral enclosure [M. Sheffield]; AJM-1 (green) and muscle (red) during elongation [P. Heid]; HMP-2/beta-catenin electrostatic surface [H.-J. Choi]; AJM-1 (green) and muscle (red) in an elongated embryo [A. Cox-Paulson]; phalloidin staining in elongated embryo [M. Costa]

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...

Postdoctoral positions available! Click here for more information…

Our work is supported by the National Institute of General Medical Sciences, NIH
NIGMSLogo_lrg
CONTACT
Jeff Hardin • Department of Integrative Biology, University of Wisconsin-Madison
327 Integrative Biology Research Building • 1117 W. Johnson St. • Madison, WI 53706
voice: (608) 262-9634 • fax: (608) 262-7319 • lab: (608) 265-2520 • email: jdhardin@wisc.edu

GRADUATE PROGRAMS
Integrative Biology  |  Biophysics  |  Cellular & Molecular Biology  |  Genetics  |  Molecular & Cellular Pharmacology

Recent News

November 2021
We've finally moved to the modern era! Please update your bookmarks from http://worms.zoology.wisc.edu to https://worms.zoology.wisc.edu
Thanks to Jon Hardin, CEO of Hardin Design and Development, for helping his dad upgrade the site.

October 2021
Welcome to Zoe Tesone (new CMB grad student) and Jon Heier (new postdoc, who joins us from Adam Kwiatkowski's lab at Pitt)! Congrats to former postdoc Joanna Bundus on becoming Vice President for Research at Xylome Corporation.
tweezing
A preprint on our collaboration with the Yan lab, Mechanobiology Institute, Singapore is now available to preview on bioRxiv: Le et al (2021). Mechano-Biochemical Regulation of the C. elegans HMP1–HMP2 protein complex. bioRxiv 2021.09.27.462086; doi: https://doi.org/10.1101/2021.09.27.462086. Link

March 2021
I (Jeff) am pleased to say that World of the Cell 10th edition has been released! Many thanks to my coauthor, James Lodolce and the Pearson team for a job well done.
WOC_10e_front_cover

SRGP-1/srGAP stabilizes adherens junctions in the C. elegans embryo (in preparation).
hmp-1_deltavh2HMP-1ΔVH2::GFP (green) in a comma stage embryo (Bethany Lucas and Xiangqiang Shao).

August 2020
The movies on this site have finally been upgraded to the modern HTML5 era! Now they can all be viewed on smart phones and tablets without QuickTime.
App Movies

Hardin, J. and Weliky, M. (2019). Cell rearrangement induced by filopodial tension accounts for the late phase of convergent extension in the sea urchin archenteron. Mol. Biol. Cell 30:1911-1919. PubMed pdf
urchin_sem_colorizedColorzed SEMs of L. pictus gastrulae (J. Hardin).

Shao, X., Lucas, B.G., Strauch, J. and Hardin, J. (2019). The adhesion modulation domain of C. elegans α-catenin regulates actin binding during morphogenesis. Mol. Biol. Cell 30:2115-2123. PubMed pdf
jc48aanti-AJM-1 (green) and HMP-1 (red) staining in a hmp-1(jc48) (a CRISPR null allele; Xiangqiang Shao).

November 2017
Tim's paper got the cover of MBoC for December 2017!
Loveless, T., Qadota, H., Benian, GM., and Hardin, J. (2017). C. elegans SORB-1 localizes to integrin adhesion sites and is required for organization of sarcomeres and mitochondria in myocytes. Mol. Bio. Cell, 28:3621-3633. PubMed pdf
MBoC_dec_2017_front-matter
October 2017
srGAP review: Lucas, B. and Hardin, J. (2017). Mind the (sr)GAP – roles of Slit-Robo GAPs in neurons, brains and beyond. J. Cell Sci. 130: 3965-3974. PubMed pdf
srGAP_review
August 2017
Fine-mapping α-/β-catenin binding interface in vitro and in vivo (with Hee-Jung Choi's group). Shao, X. Kang, H., Loveless, T., Lee, G.R., , Seok, C., Weis, W.I., and Choi, H.-J., and Hardin, J. (2017). Cell–cell adhesion in metazoans relies on evolutionarily conserved features of the α-catenin•β-catenin–binding interface. J. Biol. Chem. 292,16477–16490. PubMed pdf
lightboximage_506Surface rendering of HMP-1/α-catenin (green) and HMP-2/β-catenin (aqua). Rendering by Tim Loveless

June 2017
Student news:
Congratulations to new Genetics PhDs Drs. Bethany Lucas and Xiangqiang Shao, who both defended their theses.

May 2017

The structure of a C. elegans α-catenin. Kang et al (2017). Structural and functional characterization of Caenorhabditis elegans α-catenin reveals constitutive binding to β-catenin and actin. (with Hee-Jung Choi's group; J. Biol. Chem. 29, 7077-7086). PubMed pdf
m_domainThe N terminus (purple, yellow), M domain (green, aqua) and a homology model of the actin-binding domain (red) of HMP-1/α-catenin fitted into the SAXS envelope of HMP-1. Rendering by Hee-Jung Choi.
Click here to show/hide older news…

Older News

November 2016
Walck-Shannon et al. (2016). CDC-42 orients cell migration during epithelial intercalation in the Caenorhabditis elegans epidermis. PLOS Genetics 12(11): e1006415 PubMed pdf
cdc42_PLoS_clipConfocal images of an epidermal cytoplasmic reporter (Plbp-1::GFP) in wild-type (WT) (left) and ZF1::cdc-42; cdc-42(gk388) (right) embryos, in which there is late maternal loss of CDC-42, 45 min. after terminal division. Scale bar is 5 μm. [Elise Walck-Shannon]

February 2016
F1000 review of the cadherin/catenin complex in C. elegans. F1000Research 2015, 4(F1000 Faculty Rev):1473 (doi: 10.12688/f1000research.6866.1) PubMed pdf
10.12688_f1000research.6866.1_f1
World of the Cell 9th edition (Pearson) is out! Thanks to Marisa Otegui for the beautiful image used on the cover.
woc_9e_cover
October 2015
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 pdf
su740 HMP-2 4E gfp in zu364 bluehmp-1 mutant embryo rescued with a quadruple mutant phosphomimetic form of HMP-1 tagged with gfp (Xiangqiang Shao).

August 2015
Dorsal intercalation in C. elegans uses a conserved Trio/CARMIL system upstream of Rac and RhoG. Development 142, 3549-3560. PubMed pdf

crml-1crml-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]

July 2015
Student news:
Congratulations to Elise Walck-Shannon, who defended her thesis July 29, 2015!
Blake Martin received a Gilliam fellowship from HHMI!

March 2015
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) pdf
hmp-2_v_b-cat_smallElectrostatic representation of zebrafish β-catenin (left) and C. elegans HMP-2 (right). [Hee-Jung Choi, Bill Weis, Tim Loveless]

June 2014
imagejMinor updates to ImageJ plugins
are available. Go to the Microscopy page.


January 2014
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 pdf
Pasted Graphic

February 2013
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 pdfHMP-1_homology_modelHomology 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]

August 2012
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 pdf
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]

June 2012
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 pdf
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]

January 2012
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 pdf
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]

November 2011
α-catenin review
Maiden, S.L. and Hardin, J. (2011). The secret life of α-catenin: moonlighting during morphogenesis. J. Cell Biol. 195:543–552. PubMed pdf

January 2011

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 pdf

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]

November 2010
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 pdf f1000evaluation

November 15, 2010 cover!Embryo expressing SRGP-1::GFP (green) stained for actin (purple).The inset shows extensive induced tubulations. [Ronen Zaidel-Bar]

August 2010
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.)
PubMedpdf f1000evaluation
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August 17, 2010 cover!maiden_phalloidinColor adjusted image of a hmp-1(zu278) mutant embryo stained with phalloidin. [Stephanie Maiden].

May 2010
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.)
PubMed
randomized_divisionColor 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].