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Digits May Have Evolved by Repurposing Cloacal DNA, Nature Study Finds

CRISPR deletions in zebrafish tie a conserved Hox regulatory region to cloacal development, pointing to regulatory co‑option in the fin‑to‑limb transition.

Overview

  • An international team led by the University of Geneva reports in Nature that a conserved non‑coding regulatory landscape linked to Hox genes underpins a new model for the origin of digits.
  • Comparative genomics flagged a region involved in mouse digit development, and deleting its fish counterpart with CRISPR abolished Hox activity in the zebrafish cloaca but not in fin rays.
  • Researchers mapped equivalent cloaca‑associated regulatory sequences in gar and in mice, supporting an ancestral cloacal role for this DNA.
  • In mice, removing Hoxa13 and Hoxd13 prevents digit formation, whereas deleting the analogous upstream region in zebrafish only modestly reduced fin‑ray hox activity, indicating distinct regulatory controls.
  • The authors interpret the findings as evidence that digit programs co‑opted a cloacal regulatory architecture, while acknowledging unresolved mechanistic details and the need for broader phylogenetic tests.