Heterochronic Shift in Hox-Mediated Activation of Sonic hedgehog Leads to Morphological Changes during Fin Development

Koji Sakamoto,Haruki Ochi,Keijiro Munakata,Koh Onimaru,Mikiko Tanaka,Natsuno Suda,Mika Tamura,Vincent Laudet

doi:10.1371/journal.pone.0005121

Abstract

We explored the molecular mechanisms of morphological transformations of vertebrate paired fin/limb evolution by comparative gene expression profiling and functional analyses. In this study, we focused on the temporal differences of the onset of Sonic hedgehog (Shh) expression in paired appendages among different vertebrates. In limb buds of chick and mouse, Shh expression is activated as soon as there is a morphological bud, concomitant with Hoxd10 expression. In dogfish (Scyliorhinus canicula), however, we found that Shh was transcribed late in fin development, concomitant with Hoxd13 expression. We utilized zebrafish as a model to determine whether quantitative changes in hox expression alter the timing of shh expression in pectoral fins of zebrafish embryos. We found that the temporal shift of Shh activity altered the size of endoskeletal elements in paired fins of zebrafish and dogfish. Thus, a threshold level of hox expression determines the onset of shh expression, and the subsequent heterochronic shift of Shh activity can affect the size of the fin endoskeleton. This process may have facilitated major morphological changes in paired appendages during vertebrate limb evolution.

Highlights

There has been considerable debate regarding the fundamental mechanisms that direct morphological transformations from fins into limbs with respect to the expression patterns of 59-located Hox genes and subsequent Sonic hedgehog (Shh) expression [1,2,3]
The distal edge of S. canicula fin buds has an ectodermal structure called the apical fin fold that is similar to the apical ridge of limb buds of higher vertebrates, it is not known whether the apical fin fold produces Fibroblast growth factor (Fgf)
(1) Shh expression appears as soon as there is a morphological bud in mouse and chick embryos, whereas Shh is transcribed very late in pectoral fin buds of dogfish (S. canicula)

Summary

Introduction

There has been considerable debate regarding the fundamental mechanisms that direct morphological transformations from fins into limbs with respect to the expression patterns of 59-located Hox genes and subsequent Shh expression [1,2,3]. It is generally accepted, that, the enlargement of the fin endoskeleton along the proximal-distal axis within the lineage of basal sarcopterygians (lobe-finned fishes) results from changes in the heterochronic folding of the apical fin fold [4]; other possibilities have scarcely been discussed. Application of Shh-expressing cells or an Shh-soaked bead into the anterior margin of chick limb buds induced the same type of dose-dependent mirror-image digit patterns as a graft tissue from the polarizing region [8,11]. These results raise the possibility that the duration of exposure to Shh activity may have been critical for the morphological evolution of paired appendages

Methods

Results

Conclusion