Developmental hourglass and heterochronic shifts in fin and limb development

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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.

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.

The following data sets were generated

1. Koh Onimaru
(2019) A comparison of evolutionary changes and constraints on gene regulation between fin and limb development
NCBI Gene Expression Omnibus, GSE136445.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE136445
1. Koh Onimaru
(2020) Onimaru_et_al_Supplementary_Data
10.6084/m9.figshare.9928541).

https://figshare.com/articles/Onimaru_et_al_Supplementary_Data/9928541

The following previously published data sets were used

1. Davis CA
2. Hitz BC
3. Sloan CA
4. Chan ET
5. Davidson JM
6. Gabdank I
7. Hilton JA
8. Jain K
9. Baymuradov UK
10. Narayanan AK
11. Onate KC
12. Graham K
13. Miyasato SR
14. Dreszer TR
15. Strattan JS
16. Jolanki O
17. Tanaka FY
18. Cherry JM
(2018) 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.

https://www.encodeproject.org/
1. Nantong University
(2015) Gekko_japonicus_V1.1
GCF_001447785.1.

https://www.ncbi.nlm.nih.gov/assembly/GCF_001447785.1/
1. Broad Institute
(2011) AnoCar2.0
GCF_000090745.1.

https://www.ncbi.nlm.nih.gov/assembly/GCF_000090745.1/
1. International Crocodilian Genomes Working Group
(2009) ASM28112v4
GCF_000281125.3.

https://www.ncbi.nlm.nih.gov/assembly/GCF_000281125.3/
1. Genome Reference Consortium
(2018) GRCg6a
GCF_000002315.6.

https://www.ncbi.nlm.nih.gov/assembly/GCF_000002315.6
1. Beijing Genomics Institute
(2012) GeoFor_1.0
GCF_000277835.1.

https://www.ncbi.nlm.nih.gov/assembly/GCF_000277835.1/
1. P. sinensis genome project consortium
(2012) PelSin_1.0
GCF_000230535.1.

https://www.ncbi.nlm.nih.gov/assembly/GCF_000230535.1/
1. Painted turtle genome sequencing consortium
(2014) Chrysemys_picta_bellii-3.0.3
GCF_000241765.3.

https://www.ncbi.nlm.nih.gov/assembly/GCF_000241765.3/
1. Max Planck Society
(2018) ASM291563v1
GCA_002915635.1.

https://www.ncbi.nlm.nih.gov/assembly/GCA_002915635.1/
1. DOE Joint Genome Institute
(2016) Xenopus_tropicalis_v9.1
GCF_000004195.3.

https://www.ncbi.nlm.nih.gov/assembly/GCF_000004195.3/
1. Broad Institute
(2011) LatCha1
GCF_000225785.1.

https://www.ncbi.nlm.nih.gov/assembly/GCF_000225785.1/
1. Broad Institute
(2012) LepOcu1
GCF_000242695.1.

https://www.ncbi.nlm.nih.gov/assembly/GCF_000242695.1/
1. Genome Reference Consortium
(2017) GRCz11
GCF_000002035.6.

https://www.ncbi.nlm.nih.gov/assembly/GCF_000002035.6/
1. The University of Tokyo
(2017) ASM223467v1
GCF_002234675.1.

https://www.ncbi.nlm.nih.gov/assembly/GCF_002234675.1/
1. Institute of Molecular and Cell Biology
2. Singapore
(2013) Callorhinchus_milii-6.1.3
GCF_000165045.1.

https://www.ncbi.nlm.nih.gov/assembly/GCF_000165045.1/
(2018) Storazame_v1.0
GCA_003427355.1.

https://www.ncbi.nlm.nih.gov/genome/12714?genome_assembly_id=397946
(2018) Cpunctatum_v1.0
GCA_003427335.1.

https://www.ncbi.nlm.nih.gov/genome/12366?genome_assembly_id=397945

Article and author information

Author details

Koh Onimaru

Laboratory for Bioinformatics Research, RIKEN Center for Biosystems Dynamics Research, Wako, Japan

For correspondence
koh.onimaru@riken.jp

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2428-9510
Kaori Tatsumi

Laboratory for Phyloinformatics, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan

Competing interests
The authors declare that no competing interests exist.
Chiharu Tanegashima

Laboratory for Phyloinformatics, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan

Competing interests
The authors declare that no competing interests exist.
Mitsutaka Kadota

Phyloinformatics Unit, RIKEN Center for Life Science Technologies, 2-2-3 Minatojima-minamimachi,Chuo-ku, Japan

Competing interests
The authors declare that no competing interests exist.
Osamu Nishimura

Phyloinformatics Unit, RIKEN Center for Life Science Technologies, 2-2-3 Minatojima-minamimachi,Chuo-ku, Japan

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-1969-2580
Shigehiro Kuraku

Laboratory for Phyloinformatics, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan

For correspondence
shigehiro.kuraku@riken.jp

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-1464-8388

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).

Copyright

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.