The Hardin Lab

An elongating C. elegans embryo stained for HMP-1/α-catenin (green) and AJM-1 (red),
imaged using deconvolution microscopy [Jeff SImske].

Morphogenesis requires that cells make strong connections with one another. We are studying how the cadherin complex, which is conserved in all metazoans, regulates morphogenesis. We are using a variety of approaches to study the cadherin complex, including:

(1) Structure-function in the embryo to identify key regions in core cadherin complex proteins essential for their functions;

Point mutations in a conserved tyrosine in HMP-2/β-catenin to probe the importance of key regulatory residues.
hmp-2(Y599F)::gfp (phospho null; left)
hmp-2(Y599E)::gfp (phosphomimetic; right) constructs in a strong loss-of-function mutant for C. elegans HMP-2/β-catenin. [Tim Loveless]

(2) X-ray crystallography of the cadherin/catenin complex in collaboration with Hee-Jung Choi (Seoul National University) and BIll Weis's laboratory (Stanford University);

Electrostatic representation of zebrafish β-catenin (left) and C. elegans HMP-2 (right).
[Hee-Jung Choi, Bill Weis, Tim Loveless]

(3) Functional genomics and proteomics to identify proteins and pathways that act in concert with the cadherin complex during morphogenesis. These include actin binding proteins and the Slit/Robo GAP, SRGP-1.

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