How close are we to identifying all of the signalling pathways that are involved in neural tube patterning? The fact that the same factors keep cropping up again and again might indicate that we are getting near. For example, the signals that specify dorsal neural fates were relatively unexplored until recently, but the pathways uncovered so far consist of familiar molecules such as the Wnts and bone morphogenetic proteins (BMPs). However, as reported in Neuron, the discovery of a new signalling molecule by Tsuda et al. indicates that there might still be a few surprises in store.

The authors set out to find genes that encode secreted molecules that are involved in the patterning of the anterior central nervous system. They identified one such gene that was expressed in a crescent, or 'tiara', in the anterior ectoderm of the gastrula-stage embryo, and they named this gene Tiarin . Later in development, Tiarin was expressed in the non-neural ectoderm that flanks the prospective brain region, and transcripts were also detected in the roof plate after neural tube closure.

To investigate the activity of this new protein, Tsuda et al. took eight-cell Xenopus embryos and injected Tiarin mRNA into the cells that were fated to become neural plate. This manipulation caused an expansion of dorsal neural markers in the resulting embryos. There was no evidence of any increase in dorsal cell proliferation or ventral cell death, indicating that Tiarin is a genuine dorsalizing factor.

The authors then tested its effects on explants of uncommitted ectodermal tissue (animal caps) from blastula-stage embryos. Tiarin alone did not alter the fate of the tissue. However, if its mRNA was co-injected with that of the neuralizing factor Chordin, the caps acquired dorsal neural characteristics, whereas Chordin alone activated more ventral neural markers. So, Tiarin is not a neuralizing factor, but it can dorsalize ectoderm that has been neuralized by Chordin.

So, what is its mechanism of action? In the animal cap assay, Tiarin could override the ventralizing effect of sonic hedgehog (Shh), so it is tempting to speculate that it acts simply as a Shh antagonist. However, it was also able to dorsalize animal caps that did not express Shh, and it had no effect on the expression of downstream genes in the Shh pathway, such as Patched and Gli1. The authors also explored the possibility that Tiarin belongs to a Wnt or BMP signalling pathway, but they found that its expression had no significant effect on the activity of either of these pathways, and it also activated a different set of marker genes.

This raises the tantalizing possibility that Tiarin is part of a completely new signalling pathway that provides dorsalizing signals specifically for the brain neuroectoderm. If this is true, the identification of the other factors that participate in this pathway should provide an exciting new line of research.