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How swimming fish evolved into land-traveling, four-limbed vertebrates is a longstanding mystery.

Twelve years ago,��of the University of Chicago unearthed a 370-million-year-old����that was hailed as a “missing link” from sea to land animals.

But how, exactly, can a fin turn into a limb?

This week in��,��Shubin and colleagues report on work initiated at �������� (��������) that provides major insight into the game-changing fin-to-limb transition. Led by Tetsuya Nakamura, the team showed that a set of genes, called��Hox,��plays a surprisingly similar role in patterning the rays of fins and the digits of tetrapod limbs.����calls it the discovery of�� “a deep evolutionary connection” between fins and hands and feet.

This work was launched in the ��������’s��Whitman Center��in 2014, when Nakamura began studying the role of��Hox��genes in embryonic skates and sharks. With subsequent training in gene editing (CRISPr–Cas9) at the��National Xenopus Resource��at ��������, Nakamura created zebrafish mutants to further study��Hox.

“This extraordinary study highlights the scientific convening power of the �������� and provides an elegant example of the unique opportunities the laboratory continues to provide to young scientists to take risks and drive forward major questions in biology,” says �������� Director of Research Jonathan Gitlin.