# Deep homology of a brachyury cis-regulatory syntax and the evolutionary origin of the notochord

## TL;DR

This study reveals an ancient gene regulatory code that may explain how the notochord evolved from gut cells in early animals.

## Contribution

The discovery of a conserved regulatory syntax (SFZE) linked to brachyury across diverse species, including unicellular relatives of animals.

## Key findings

- The SFZE regulatory syntax is present in brachyury enhancers across chordates and non-chordates.
- Non-chordate SFZE enhancers show activity in the zebrafish notochord.
- SFZE predates animals and may have facilitated the origin of the notochord from endodermal cells.

## Abstract

Expression of brachyury in the notochord is regarded as a chordate novelty and links to the origin of the notochord, yet the evolution of this regulatory control remains unclear. Here, we uncovered a regulatory syntax (named SFZE) consisting of binding sites for four transcription factors in notochord enhancers of chordate brachyury genes. SFZE was also identified in potential brachyury enhancers in various non-chordate animals and even in Capsaspora, a unicellular relative to animals. These non-chordate SFZE-containing enhancers exhibited activity in the zebrafish notochord. Furthermore, the SFZE syntax in a non-chordate confers endoderm activity. Our results indicate the ancient association of SFZE with brachyury, likely predating the origin of animals. The emergence of notochordal brachyury expression could be attributed to co-option of upstream signals acting on the conserved SFZE syntax, which facilitates the origin of the notochord from rudimentary endodermal cells.

An ancient gene regulatory code facilitates the origin of the notochord from rudimentary gut cells by recruiting upstream factors.