Overview

• An international team led by the University of Geneva reports in Nature that digit development likely co-opted an ancient non-coding region originally active in the fish cloaca.
• Comparative genomics identified a conserved regulatory landscape linked to Hox gene activation in mouse digits but, when deleted in zebrafish, it abolished cloacal expression without stopping fin expression.
• The zebrafish deletions produced only a modest reduction of fin Hox activity, indicating that fish fin rays and tetrapod digits use different regulatory mechanisms to activate similar genes.
• Equivalent regulatory regions were documented in mice and in gar, supporting deep conservation of the cloacal control sequences across vertebrates.
• The findings reframe digit origins as evolutionary recycling of a cloacal regulatory program, consistent with prior work showing Hoxa13/Hoxd13 are essential for mouse digit formation.