Digits and fin rays share common developmental histories

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Understanding the evolutionary transformation of fish fins into tetrapod limbs is a fundamental problem in biology1. The search for antecedents of tetrapod digits in fish has remained controversial because the distal skeletons of limbs and fins differ structurally, developmentally, and histologically2,3. Moreover, comparisons of fins with limbs have been limited by a relative paucity of data on the cellular and molecular processes underlying the development of the fin skeleton. Here, we provide a functional analysis, using CRISPR/Cas9 and fate mapping, of 5′hoxgenes and enhancers in zebrafish that are indispensable for the development of the wrists and digits of tetrapods4,5. We show that cells marked by the activity of an autopodialhoxa13enhancer exclusively form elements of the fin fold, including the osteoblasts of the dermal rays. Inhox13knockout fish, we find that a marked reduction and loss of fin rays is associated with an increased number of endochondral distal radials. These discoveries reveal a cellular and genetic connection between the fin rays of fish and the digits of tetrapods and suggest that digits originated via the transition of distal cellular fates.

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