Sci Adv 2025 Jan 24;114:eadq4731. doi: 10.1126/sciadv.adq4731.

An ancient apical patterning system sets the position of the forebrain in chordates.

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The evolutionary origin of the vertebrate brain remains a major subject of debate, as its development from a dorsal tubular neuroepithelium is unique to chordates. To shed light on the evolutionary emergence of the vertebrate brain, we compared anterior neuroectoderm development across deuterostome species, using available single-cell datasets from sea urchin, amphioxus, and zebrafish embryos. We identified a conserved gene co-expression module, comparable to the anterior gene regulatory network (aGRN) controlling apical organ development in ambulacrarians, and spatially mapped it by multiplexed in situ hybridization to the developing retina and hypothalamus of chordates. Using functional approaches, we show Wnt signaling regulating this co-expression module in amphioxus, like the aGRN in echinoderms, and that its overactivation suppresses forebrain identity. This suggests a previously undescribed role for Wnt signaling in amphioxus in determining the position of the forebrain. We propose this Wnt-regulated gene co-expression module as a possible mechanism by which the brain set antero-dorsally early in chordate evolution.

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