Research based in the Department of Zoology has potentially advanced the resolution of one of evolutionary biology’s greatest mysteries: how our complex brains evolved from simpler nervous systems.

The research is described in a new paper, ‘An ancient apical patterning system sets the position of the forebrain in chordates’, published in Science Advances in January 2025, authored by Giacomo Gattoni, a recipient of a Whitten Trust award, Daniel Keitley, a Wellcome Trust fellow and Dr Èlia Benito-Gutiérrez (corresponding author).

The vertebrate brain is strikingly different from the brains of other animals like flies or worms, making it challenging to explain the evolutionary link. Our brain is located on the back of the body and has a tubular structure. In contrast, a fruit fly's brain is on its belly and consists of tracks of nerve fibres. For decades, scientists have been formulating hypotheses about how the transition from a fly-like brain to a mouse-like brain could have happened.

In their study, Dr Benito-Gutiérrez’s group investigated the genetic activity of individual cells from sea urchin, amphioxus, and zebrafish embryos. These three species occupy key positions in the evolutionary tree, making them ideal for addressing this question. They discovered a conserved set of genes that work together to specify neurosecretory cells in all three species, but with a fascinating twist: In sea urchins, these cells become part of the apical organ (a sensory neurosecretory organ), while in amphioxus and zebrafish, they develop as part of the anterior brain, specifically in the retina and hypothalamus. 

The development of the apical organ is controlled by a very ancient gene regulatory network, present even in jellyfish. This ancient network includes the genes they identified in their study, but importantly, it's under the control of a diffusible molecule called Wnt. 

Wnt allows the network to be territorially restricted during the development of planktonic larvae to form the neurosecretory organ. They found that amphioxus uses this same system to territorially restrict the site where its brain will form. 

This provides compelling evidence that this ancestral gene regulatory network was repurposed through evolution to contribute to the revolutionary innovation of forming a dorsal tubular brain, likely around the time of the evolutionary origin of chordates.
 

Giacomo Gattoni, Daniel Keitley, Ashley Sawle , and Elia Benito-Gutiérrez. An ancient apical patterning system sets the position of the forebrain in chordates. Sci. Adv.11,eadq4731(2025).DOI:10.1126/sciadv.adq4731