Evolution of Vertebrate Limb Development


The origin and diversification of fins and limbs have long been a focus of interest to both palaeontologists and developmental biologists. Studies conducted in recent decades have resulted in enormous progress in the understanding of the genetic and developmental bases of the evolution of paired appendages in vertebrates. These discoveries in the areas of genetics and developmental biology have shed light on the mechanisms underlying the evolution of this key morphological innovation in vertebrates. In this article, recent advances in these fields and how they can provide a mechanistic explanation for the origin and evolution of paired appendages have been discussed.

Key Concepts

  • Step‐wise changes seem to be involved in the acquisition of paired fins, such as regionalisation of the lateral plate mesoderm (LPM) into the anterior and posterior LPM; sub‐division of the LPM into somatic and splanchnic layers; acquisition of expression of genes that initiate limb formation, such as Tbx4/5; and dorso‐ventral compartmentalisation of ectoderm.
  • Morphological changes during the fin‐to‐limb transition include the acquisition of the autopod and the evolutionary modification of skeletal patterns along the anterior–posterior axis.
  • The fin‐to‐limb transition seems to involve changes in transcriptional regulation of HoxA and HoxD clusters, changes in the expression of Gli3 and Shh, loss of the fin fold, and modification of the BMP‐SOX9‐WNT Turing network.
  • Changes in the activity of regulatory elements of genes known to play pivotal roles in limb development seem to be related to the morphological diversification of limbs and the loss of paired fins and limbs.

Keywords: limb; fin; evolution; vertebrates; lateral plate mesoderm

Figure 1. Models for the evolution of paired appendages in vertebrates. (a) The ‘lateral fin fold theory’, in which two paired appendages evolved from a continuous lateral fin, was proposed by Thacher ; Mivart and Balfour . (b) The ‘pelvic before pectoral fin’ model suggested that the co‐option of collinear expression of Hox (green bars) from the body axis in paired appendages originated in the pelvic appendage. In this model, pelvic Hox expression was subsequently co‐opted for the development of the pectoral appendage (Tabin and Laufer, ). (c) The ‘pectoral before pelvic fin’ model was advocated based on fossil records and on the general anterior–posterior gradient of development (Coates, ; Thorogood and Ferretti, ). (d) The molecular mechanisms of fin development in paired appendages have been proposed to be adopted from the median fins (Freitas et al., ). This view was based on the observation that Hoxd genes (green bars) were expressed in a nested manner in the developing shark median fin, as seen in the paired appendages. (e) Two alternative models for the evolution of paired appendages proposed by Ruvinsky and Gibson‐Brown highlighted the coevolution of the T‐box gene with Pitx1. Initially, an ancestral jawless vertebrate acquired a novel expression domain of Tbx4/5 (purple) in the lateral plate mesoderm at the pectoral level, and this led to the formation of the first pair of fins (top). Then two alternative scenarios were considered: the T‐box cluster underwent duplication, and Tbx4 (red) and Tbx5 (blue) were co‐expressed in a single pair of fins (left middle). Subsequently, Tbx4 (red) acquired the novel expression domain in the body wall at the pelvic level (bottom). Alternatively, Tbx4/5 (purple) acquired a novel expression domain in the posterior part of the lateral plate mesoderm (right middle), and then Tbx4/5 underwent duplication and gave rise to pectoral (blue) and pelvic fins (red) (bottom). According to this model, posteriorly expressed Pitx1 (yellow) modified the identity of the posterior/pelvic appendages together with Tbx4. (f) Schematic model for regionalisation and differentiation of the ventral mesoderm and the lateral plate mesoderm (LPM) in amphioxus, lampreys and representative gnathostomes, as proposed by Onimaru et al. . Purple, orange and light blue bars represent the pharyngeal mesoderm (ph), the anterior LPM (ALPM) and the posterior LPM (PLPM), respectively. Double‐headed arrows indicate the somatic mesodermal layer. Distribution of Tbx4/5 (purple) in amphioxus and lampreys, Tbx5 (blue) in gnathostomes, and collinear Hox genes (green bars) in lampreys and gnathostomes are indicated in each embryo. vmp, ventral mesoderm posterior to the pharynx. Schematic modified from Onimaru et al. and Tanaka . Models in panels A–F were proposed by Jarvik ; Tabin and Laufer ; Thorogood and Ferretti ; Ruvinsky and Gibson‐Brown , and Onimaru et al. , respectively.
Figure 2. Expression and regulation of 5'Hox genes. (a) Schematic illustration of the early (top) and late (bottom) phases of 5'Hoxa (magenta) and 5'Hoxd (blue) genes in mouse forelimb buds. Expression patterns of 5'Hox genes were re‐drawn and modified after Dolle et al. . (b) Model for the regulatory evolution of HoxA and HoxD genes during the fin‐to‐limb transition proposed by Woltering et al. . Coloured shapes located in the 5′ and 3′ regions of each Hox gene cluster (black rectangle) indicate enhancers, and arrows indicate the interactions between these enhancers and the Hox cluster. In fish fins, this interaction may pattern the proximal (red) and distal (orange) skeletal elements. In tetrapod limbs, new enhancers have been acquired or existing ones were modified, and thereby, a novel and more distal autopodial identity may have evolved. Redrawn and modified after Woltering et al. published by PLOS licensed in accordance with the Creative Commons Attribution (CC BY) license.
Figure 3. Skeletal patterns of anterior appendages of catshark S. canicula, Eusthenopteron, Panderichthys, Tiktaalik, Acanthostega and mouse. Grey bones indicate the basal metapterygium and humerus. Note that S. canicula has tri‐basal pectoral fins. R, radius; U, ulna. Adapted from Onimaru et al., , Johanson et al., , Boisvert et al., and Shubin et al., .
Figure 4. Schematic diagrams of expression patterns of genes involved in anterior–posterior patterning in S. canicula pectoral fin buds and mouse forelimb buds. (a) Gli3 (orange) is highly expressed in the posterior region of S. canicula pectoral fin buds. In contrast, Gli3 is highly expressed in the anterior region of murine forelimb buds. (b) The Alx4 (pink)/Pax9 (light blue) anterior domain is more extensive in S. canicula pectoral fin buds than in murine forelimb buds. (c) Skeletal pattern of S. canicula pectoral fin and mouse forelimb. Grey elements are the pro‐ and mesopterygium. Purple bones indicate the basal metapterygium/humerus. Expression patterns were re‐drawn from previous work: S. canicula (Onimaru et al., ) and mouse (Fernandez‐Teran et al., ; McGlinn et al., ; Yokoyama et al., ; Galli et al., ). See text for additional references and details.


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Further Reading

Tickle C (2016) Vertebrate embryo: limb development. In: Encyclopedia of Life Sciences. Chichester: John Wiley & Sons, Ltd. ISBN: 10.1002/9780470015902.a0000728.pub2.

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Tanaka, Mikiko(Sep 2017) Evolution of Vertebrate Limb Development. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002099.pub2]