title: Digits and fin rays share common developmental histories.
abstract: Understanding the evolutionary transformation of fish fins into tetrapod limbs is a fundamental problem in biology. The search for antecedents of tetrapod digits in fish has remained controversial because the distal skeletons of limbs and fins differ structurally, developmentally, and histologically. 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' hox genes and enhancers in zebrafish that are indispensable for the development of the wrists and digits of tetrapods. We show that cells marked by the activity of an autopodial hoxa13 enhancer exclusively form elements of the fin fold, including the osteoblasts of the dermal rays. In hox13 knockout 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.
authors.affiliation: Department of Organismal Biology and Anatomy, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Organismal Biology and Anatomy, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gehrke
authors.affiliation: Department of Organismal Biology and Anatomy, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Lemberg
authors.affiliation: Department of Organismal Biology and Anatomy, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Szymaszek
authors.affiliation: Department of Organismal Biology and Anatomy, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Neil H
authors.initials: NH
authors.lastname: Shubin
mesh_terms: D058500:Animal Fins / Q000196:embryology* / Q000378:metabolism; D000818:Animals; D005075:Biological Evolution; D019070:Cell Lineage; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005121:Extremities / Q000196:embryology*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D005810:Multigene Family / Q000235:genetics; D010641:Phenotype; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C099959:homeobox protein HOXA13