We have shown that during amphibian development, dishevelled (Xdsh) signaling controls the convergent extension of neural tissues, and that loss of Xdsh function results in a failure of neural tube closure (seeDevelopment 129, 5815-5825 and Development, 128, 2581-2592 ). Time-lapse microscopy (see movies here!) and targeted injections revealed that Xdsh signaling is not required for neural fold elevation, medial movement, or fusion. Disruption of Xdsh signaling therefore provides a specific tool for uncoupling convergent extension from other processes of neurulation. Using disruption of Xdsh signaling, we demonstrate that convergent extension is critical to tube closure.

Our data indicate that the inherent movement of the neural folds can accomplish only a finite amount of medial progress and that converegnt extension of the midline is necessary to reduce the distance between the nascent neural folds, allowing them to meet and fuse. Because human embryos with craniorachischisis and mice in which PCP signaling has been disrupted also display shortened axes and broad, open neural tubes, our data suggest that this type of neural tube defect may result generally from a failure of convergent extension.

We are continuing these studies and are also now examining molecules that control other critical events during neurulation. For these studies we are taking advantage of the axolotl, Ambystoma mexicanum. Axolotl neurulation is quite robust and closely resembles mammalian neurulation. Becasue the axolotl is amenable to the same manipulations as Xenopus, we hope that this embryo will help us to discern the details of neural tube closure.