Developmental hourglass and heterochronic shifts in fin and limb development
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.
Data availability
RNA-seq and ATAC-seq datasets generated during the current study are available in the Gene Expression Omnibus (GEO) repository under accession number GSE136445. Data to reproduce this study are deposited in figshare (https://figshare.com/articles/Onimaru_et_al_Supplementary_Data/9928541; DOI: 10.6084/m9.figshare.9928541). Code for clustering analysis is available at https://github.com/koonimaru/easy_heatmapper.
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A comparison of evolutionary changes and constraints on gene regulation between fin and limb developmentNCBI Gene Expression Omnibus, GSE136445.
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Onimaru_et_al_Supplementary_Data10.6084/m9.figshare.9928541).
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The Encyclopedia of DNA elements (ENCODE): Data portal update.ENCFF478FHR ENCFF955MIX ENCFF210MKE ENCFF431KXE ENCFF275OKU ENCFF426VDN ENCFF002LRT ENCFF576SKK ENCFF592ZRO ENCFF798QON ENCFF336VLY ENCFF407NCE ENCFF572CMB ENCFF695FLH ENCFF130WMA ENCFF224JRS ENCFF337ETV ENCFF535DAV ENCFF540ZEZ ENCFF762LUG ENCFF279LMU ENCFF518FYP ENCFF377YCK ENCFF086MTT ENCFF064NKM ENCFF406EUS ENCFF258GFE ENCFF031SEH ENCFF694SPD ENCFF051GLX ENCFF304CCF ENCFF655OFT ENCFF483MKX ENCFF007HEF ENCFF550NVA ENCFF848NLJ ENCFF929LOH ENCFF382CMV ENCFF360MVK ENCFF159HYY ENCFF618OJP ENCFF329VCX ENCFF341HRL ENCFF894ZND ENCFF702NAP ENCFF109LQF ENCFF146ZCO ENCFF154RTC ENCFF709ZKC ENCFF040SPZ ENCFF912PDM ENCFF141JSP ENCFF985YPA ENCFF064JRU ENCFF774MTJ ENCFF376TIM ENCFF612QXM ENCFF584HRP ENCFF353TSI ENCFF583FIG ENCFF143XEE ENCFF590KVK ENCFF107GOQ ENCFF370RSB ENCFF906UHI ENCFF034BFB ENCFF928FUL ENCFF872PTK ENCFF982ZSW ENCFF454BSG ENCFF035UJZ ENCFF471VWH ENCFF501QKH ENCFF113PQF ENCFF322CQL ENCFF622HGW ENCFF746ASR ENCFF232GHI ENCFF484RFZ ENCFF658OKS ENCFF232PNH ENCFF403VCU ENCFF688KUB ENCFF815LLD ENCFF557YZH ENCFF636YTN ENCFF142IPK ENCFF387ORM ENCFF877QHQ ENCFF877LFX ENCFF994LOF ENCFF398KDL ENCFF618YMO ENCFF598ZGD ENCFF924SYL ENCFF809YXL ENCFF685HFN ENCFF697FTK ENCFF887QYY ENCFF171GOW ENCFF790TWE ENCFF635MWR ENCFF818OKO ENCFF978ZGA ENCFF645HNE ENCFF237MEG ENCFF738MPC ENCFF905ZTZ ENCFF914USA ENCFF417HDL ENCFF105XRN ENCFF302YAI ENCFF502HEW ENCFF978POS ENCFF107SIK ENCFF143SWD ENCFF311YQH ENCFF940KCT.
Article and author information
Author details
Funding
Japan Society for the Promotion of Science (17K15132)
- Koh Onimaru
Ministry of Education, Culture, Sports, Science and Technology (N/A)
- Koh Onimaru
- Kaori Tatsumi
- Chiharu Tanegashima
- Mitsutaka Kadota
- Osamu Nishimura
- Shigehiro Kuraku
RIKEN (N/A)
- Koh Onimaru
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal experiments were conducted in accordance with the guidelines approved by the Institutional Animal Care and Use Committee (IACUC), RIKEN Kobe Branch, and experiments involving mice were approved by IACUC (K2017-ER032).
Reviewing Editor
- Karen E Sears, University of California, Los Angeles, United States
Version history
- Received: September 7, 2020
- Accepted: February 1, 2021
- Accepted Manuscript published: February 9, 2021 (version 1)
- Version of Record published: March 4, 2021 (version 2)
Copyright
© 2021, Onimaru et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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