Transverse section of a normal Xenopus embryo, showing elevated neural folds. Courtesy of J. Wallingford, Department of Molecular and Cell Biology, University of California, Berkeley, USA.

In vertebrate embryos, the process of neurulation, which transforms a flat neural plate into a three-dimensionally patterned tube, relies on a sequence of morphogenetic events that are tightly coordinated with cell proliferation. Changes in cell shape cause the neuroepithelium to thicken, and the neural folds to elevate and acquire a concave profile. Continued cell shape changes and expansion of the flanking epidermis help to push the lateral edges of the neural plate together to allow fusion to occur. Writing in Development, Wallingford and Harland now highlight the importance of another process — convergent extension — in neural tube closure.

Convergent extension is a two-dimensional cellular rearrangement, in which a tissue elongates along one axis while simultaneously narrowing at right angles to that axis (imagine a crowd of marathon runners converging into a narrow column as they cross the starting line). The authors previously showed that in Xenopus, the signal transduction molecule Dishevelled (Xdsh) is required both for convergent extension and neural tube closure, but the relationship between these two events remained unclear.

Wallingford and Harland inactivated Xdsh by injecting a mutant form of the Xdsh gene into Xenopus embryos. Using histological techniques and time-lapse photography they examined the effects on neurulation. They found that most of the mechanisms that are involved in neurulation, including elevation and medial movement of the neural folds, still occurred normally, but in many embryos the neural tube failed to close. Interestingly, however, Xdsh function at the lateral edges of the neural folds was not necessary for neural tube closure. Rather, it seemed to function within the medial portion of the neural plate.

Evidence that convergent extension was contributing to neural tube closure came from the observation that the closure defect was associated with a reduced elongation of the neural tube, and the elevated neural folds remained further apart than in control embryos. In normal embryos, the midline marker netrin is initially expressed in a broad medial band along the anteroposterior axis of the neural plate, and this band becomes longer and narrower as neurulation proceeds. When Xdsh function was blocked, the netrin expression domain failed to undergo this change. Taken together, these findings indicate that the shaping of the midline through convergent extension is an integral part of the neural tube closure mechanism.

So, changes in neuroepithelial cell morphology and medial movements of the neural folds are insufficient to bring about neural tube closure on their own, and convergent extension can provide the additional force that is required to draw the lateral edges of the neural folds together. In humans, neural tube defects are among the most common birth defects — by increasing our understanding of the mechanisms that underlie neurulation, it should be possible to develop more effective treatments and preventive measures.