During early embryogenesis, morphogen gradients specify the neural plate along the anterior-posterior axis. Canonical Wnt signalling causes the posteriorization of neural tissues. Consequently, Wnt signal attenuation in the embryo's anterior region is required for the determination of the head region; but how is this achieved? On p. 3293, Hidehiko Inomata, Yoshiki Sasai and co-workers reveal that modulation of canonical Wnt signalling by the extracellular matrix protein Del1 (Developmental endothelial locus-1) is essential for forebrain development in Xenopus embryos. Del1 overexpression expands the forebrain domain, the researchers report, whereas Del1 functional inhibition represses forebrain development. They show that Del1 function in neural plate patterning is mediated mainly by inhibition of canonical Wnt signalling downstream of β-catenin. Notably, however, Del1 inhibition of canonical Wnt signalling involves the Ror2 (receptor tyrosine kinase-like orphan receptor 2) pathway, which is implicated in non-canonical Wnt signalling. These data suggest that Del1 promotes forebrain development by creating a local environment that attenuates the cellular response to Wnt signals via a unique pathway.
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