Developmental hourglass and heterochronic shifts in fin and limb development.

Shigehiro Kuraku,Mitsutaka Kadota,Osamu Nishimura,Chiharu Tanegashima,Koh Onimaru,Kaori Tatsumi

doi:10.7554/elife.62865

Shigehiro Kuraku, Mitsutaka Kadota + Show 4 more

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https://doi.org/10.7554/elife.62865

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Abstract

How genetic changes are linked to morphological novelties and developmental constraints remains elusive. Here, we investigate genetic apparatuses that distinguish fish fins from tetrapod limbs by analyzing transcriptomes and open-chromatin regions (OCRs). Specifically, we compared mouse forelimb buds with the pectoral fin buds of an elasmobranch, the brown-banded bamboo shark (Chiloscyllium punctatum). A transcriptomic comparison with an accurate orthology map revealed both a mass heterochrony and hourglass-shaped conservation of gene expression between fins and limbs. Furthermore, open-chromatin analysis suggested that access to conserved regulatory sequences is transiently increased during mid-stage limb development. During this stage, stage-specific and tissue-specific OCRs were also enriched. Together, early and late stages of fin/limb development are more permissive to mutations than middle stages, which may have contributed to major morphological changes during the fin-to-limb evolution. We hypothesize that the middle stages are constrained by regulatory complexity that results from dynamic and tissue-specific transcriptional controls.

Highlights

28 IntroductionThe genetic mechanism of morphological diversity among multicellular organisms is of central interest in evolutionary biology
The simplest hypothesis for this mass heterochronic shift is that the later stages of limb development gained expression of one or a few upstream transcription factor(s) or signaling molecules that collectively regulate this group of genes
Because SHH-independent regulation of its target genes through the GLI3-HOX complex was previously reported (Chen et al, 2004), the mismatch between the peak expression of Shh and its target genes may be caused by such SHH-independent regulatory mechanisms that are absent in bamboo shark fin development

Summary

13 Abstract

How genetic changes are linked to morphological novelties and developmental constraints remains elusive. We investigate genetic apparatuses that distinguish fish fins from tetrapod limbs by analyzing transcriptomes and open chromatin regions (OCRs). Open-chromatin analysis suggested that access to conserved regulatory sequences is transiently increased during mid-stage limb development. During this stage, stage-specific and tissue-specific OCRs were enriched. Early and late stages of fin/limb development are more permissive to mutations than middle stages, which may have contributed to major morphological changes during the fin-to-limb evolution. We hypothesize that the middle stages are constrained by regulatory complexity that results from dynamic and tissue-specific 25 transcriptional controls

28 Introduction

Results

Discussion

Materials and Methods