On Sunday afternoon at ASCB 2015, I attended the minisymposium on Cell Migration in Tissues. It was a terrific session that covered a wide range of migratory behaviors in development, disease, and repair. Here, I’ll focus on the stories that have already been published, though there was plenty of great unpublished work presented as well.
Celeste Nelson (Princeton) described the use of microfabricated tissues and 3D traction force microscopy to study the forces generated by mammary epithelial cells during branching morphogenesis, demonstrating that branch extension is associated with high contractile forces at the leading edge of new branches. These forces pull on the surrounding extracellular matrix and align its fibers into tracks that guide the collective migration of the mammary cells as they form the new branch.
David Matus (Stony Brook) discussed his recent paper exploring the mechanisms that control anchor cell invasion in C. elegans. During the worm’s development, this specialized uterine cell breaks through a basement membrane to connect to the underlying vulval tissue. Because this event can be visualized by live imaging in vivo, it’s a terrific model system for studying cell invasion (a key step in cancer metastasis). Matus and colleagues found that anchor cells must arrest in G1 before they can become invasive; in the absence of the transcription factor NHR-67, cells continue to proliferate and don’t invade. It will certainly be interesting to see if similar rules apply in cancer, such that metastasis is driven by non-proliferative tumor cells.
Eliah Shamir, from Andrew Ewald’s lab at Johns Hopkins School of Medicine, gave a terrific talk expanding on her 2014 JCB paper describing the role of the transcription factor Twist1 in promoting the dissemination of single cells from 3D organotypic cultures (and the surprising finding that, contrary to the usual model of epithelial-to-mesenchymal transitions, the disseminating cells retain their epithelial character and that the cell adhesion molecule E-cadherin promotes their dispersal).
Bong Hwan Sung, from Alissa Weaver’s lab at Vanderbilt University School of Medicine gave a fascinating presentation describing how cancer cells enhance their directional migration through tissues by secreting exosomes. These small, extracellular vesicles are coated with the extracellular matrix protein fibronectin and so they promote adhesion assembly and stabilize cell protrusions.
And Micah Webster, from Chen-Ming Fan’s group at the Carnegie Institution of Science, described his hot-off-the-press paper examining the in vivo movements of satellite stem cells during muscle regeneration. When muscle fibers are injured, they degenerate until all that remains are remnants of the basal lamina that surrounded them. Webster et al. found that these “ghost fibers” guide the migration and proliferation of satellite cells as they repair the injured muscle. The stem cells migrated back and forth along the long axis of ghost fibers (see the video above), and divided in this direction as well. Webster and colleagues think that this may help the cells spread out evenly so that they can then fuse together and differentiate into a new muscle fiber.
Intravital imaging video of satellite cells during muscle regeneration courtesy of Micah Webster et al.
Top image of Twist1-expressing cells (green) disseminating from an explanted mammary duct © 2014 Shamir et al.