Epiblast cells CLASP onto the basement membrane

Nakaya et al. reveal how the microtubule plus-end tracking protein CLASP and the adhesion receptor Dystroglycan combine to regulate epithelial-to-mesenchymal transitions (EMTs) in early embryogenesis.

During gastrulation, cells in the primitive streak—part of an epithelial layer called the epiblast—undergo EMT to form the embryonic mesoderm. One of the first steps in this process is the destabilization of basal microtubules that promote epiblast cells’ attachments to the underlying basement membrane (BM). As a result, cell adhesion is weakened and the BM disassembles. Nakaya et al. wondered whether microtubule plus end–binding proteins called CLASPs, which anchor microtubules to the cortex of other epithelial cells in culture, might be involved in regulating epiblast adhesion and EMT.

CLASPs were down-regulated in the primitive streak of chick embryos at the onset of gastrulation. Overexpressing CLASP inhibited BM breakdown, whereas depleting the protein prompted BM disassembly in regions outside the primitive streak. Basal microtubules were destabilized in the absence of CLASP and its binding partners LL5α and LL5β.

Nakaya et al. found that CLASP interacted with Dystroglycan and that this transmembrane protein, which binds to BM components such as laminin, was down-regulated in cells lacking CLASP. Overexpressing Dystroglycan prevented BM disassembly, whereas Dystroglycan depletion stimulated BM breakdown. CLASP and Dystroglycan therefore promote epiblast cell–BM attachments by anchoring basal microtubules. Senior author Guojun Sheng now wants to investigate why the BM disassembles when this connection is disrupted at the onset of gastrulation.