Details of the Researcher

PHOTO

Masahiro Uesaka
Section
Graduate School of Life Sciences
Job title
Assistant Professor
Degree

Research History 5

  • 2024/07 - Present
    Tohoku University

  • 2022/09 - Present
    Tohoku University　Graduate School of Life Sciences　Assistant Professor

  • 2018/04 - 2022/08
    RIKEN Center for Biosystems Dynamics Research　Research scientist

  • 2015/04 - 2018/03
    Graduate School of Science, The University of Tokyo　JSPS Research Fellow (PD)

  • 2012/04 - 2015/03
    JSPS　Research Fellow (DC1)

Education 1

  • 京都大学 大学院理学研究科 生物科学専攻 博士課程

    2012/04 - 2015/03

Research Interests 8

  • Vertebrate

  • Epigenome

  • Transcriptome

  • ATAC-seq

  • Developmental hourglass model

  • Recapitulation theory

  • EvoDevo

  • Evolutionary developmental biology

Research Areas 3

  • Life sciences / Molecular biology /

  • Life sciences / Developmental biology /

  • Life sciences / Evolutionary biology /

Awards 1

  1. 研究奨励賞

    2022/12　東北大学 大学院生命科学研究科

Papers 23

  1. Actinotrichia-independent developmental mechanisms of spiny rays facilitate the morphological diversification of Acanthomorpha fish fins Peer-reviewed

    Kazuhide Miyamoto, Junpei Kuroda, Satomi Kamimura, Yasuyuki Sasano, Gembu Abe, Satoshi Ansai, Noriko Funayama, Masahiro Uesaka, Koji Tamura

    Nature Communications　17　(1)　2026/02/14

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41467-026-69180-y 　

    eISSN： 2041-1723

    More details Close

    Abstract Skeletal forms in vertebrates have been regarded as good models of morphological diversification. Fish fins show great diversity in form, with their supporting skeletal structure being classified into soft rays and spiny rays. In fish evolution, spiny-ray morphologies are known to be sometimes extremely modified; however, it remains unknown how the developmental mechanisms of spiny rays have contributed to their morphological diversification. By using the rainbowfish Melanotaenia praecox for examination of the extracellular matrix (ECM) and cell dynamics of spiny-ray development, we demonstrate that spiny-ray development is independent of the actinotrichia (needle-shaped collagen polymers at the tip of fins), which are known as an important ECM in soft-ray morphogenesis. Furthermore, we found that in the thorny spiny ray of the filefish Stephanolepis cirrhifer , the lateral protrusions are associated with BMP-positive osteoblast condensation, as in the spiny-ray tips in M. praecox and S. cirrhifer . Taken together, our findings reveal that osteoblast distribution and signaling-molecule intensity would contribute to spiny-ray modification. In comparison to soft ray development, the independence from actinotrichia in spiny rays would facilitate growth direction change, leading to their morphological diversification. This suggests that variation in cell distribution and ECM usage may be important contributors to morphological diversification, not only in Acanthomorpha, but also in other animal taxa.

  2. Ontogenic Development of the Acrocoracoid Process Responsible for the Evolution of Avian Flapping Flight

    Yawara Takeda, Taira Kuramoto-Ahuja, Sayuri Yonei-Tamura, Hirotoshi Shibuya, Masaru Tamura, Masahiro Uesaka, Koji Tamura

    Zoological Science　43　(1)　2026/01/14

    Publisher: Zoological Society of Japan

    DOI： 10.2108/zs250113 　

    ISSN： 0289-0003

  3. Genomic screening of fish‐specific genes in gnathostomes and their functions in fin development Peer-reviewed

    Hidehiro Kudoh, Sayuri Yonei‐Tamura, Gembu Abe, Junichi Iwakiri, Masahiro Uesaka, Takashi Makino, Koji Tamura

    Development, Growth & Differentiation　2024/03/04

    Publisher: Wiley

    DOI： 10.1111/dgd.12918 　

    ISSN： 0012-1592

    eISSN： 1440-169X

    More details Close

    Abstract In this study, we comprehensively searched for fish‐specific genes in gnathostomes that contribute to development of the fin, a fish‐specific trait. Many previous reports suggested that animal group‐specific genes are often important for group‐specific traits. Clarifying the roles of fish‐specific genes in fin development of gnathostomes, for example, can help elucidate the mechanisms underlying the formation of this trait. We first identified 91 fish‐specific genes in gnathostomes by comparing the gene repertoire in 16 fish and 35 tetrapod species. RNA‐seq analysis narrowed down the 91 candidates to 33 genes that were expressed in the developing pectoral fin. We analyzed the functions of approximately half of the candidate genes by loss‐of‐function analysis in zebrafish. We found that some of the fish‐specific and fin development‐related genes, including fgf24 and and1/and2, play roles in fin development. In particular, the newly identified fish‐specific gene qkia is expressed in the developing fin muscle and contributes to muscle morphogenesis in the pectoral fin as well as body trunk. These results indicate that the strategy of identifying animal group‐specific genes is functional and useful. The methods applied here could be used in future studies to identify trait‐associated genes in other animal groups.

  4. Hagfish genome elucidates vertebrate whole-genome duplication events and their evolutionary consequences Peer-reviewed

    Daqi Yu, Yandong Ren, Masahiro Uesaka, Alan J. S. Beavan, Matthieu Muffato, Jieyu Shen, Yongxin Li, Iori Sato, Wenting Wan, James Clark, Joseph Keating, Emily M. Carlisle, Richard Dearden, Sam Giles, Emma Randle, Robert Sansom, Roberto Feuda, James F. Fleming, Fumiaki Sugahara, Carla Cummins, Mateus Patricio, Wasiu Akanni, Salvatore D’Aniello, Cristiano Bertolucci, Naoki Irie, Cantas Alev, Guojun Sheng, Alex de Mendoza, Ignacio Maeso, Manuel Irimia, Bastian Fromm, Kevin J. Peterson, Sabyasachi Das, Masayuki Hirano, Jonathan P. Rast, Max Cooper, Jordi Paps, Davide Pisani, Shigeru Kuratani, Fergal Martin, Wen Wang, Philip Donoghue, Yong E. Zhang, Juan Pascual-Anaya

    Nature Ecology & Evolution　2024/01/12

    DOI： 10.1038/s41559-023-02299-z 　

    ISSN： 2397-334X

  5. Distinguishing Evolutionary Conservation from Derivedness. International-journal Invited Peer-reviewed

    Jason Cheok Kuan Leong, Masahiro Uesaka, Naoki Irie

    Life (Basel, Switzerland)　12　(3)　2022/03/17

    DOI： 10.3390/life12030440 　

    More details Close

    While the concept of "evolutionary conservation" has enabled biologists to explain many ancestral features and traits, it has also frequently been misused to evaluate the degree of changes from a common ancestor, or "derivedness". We propose that the distinction of these two concepts allows us to properly understand phenotypic and organismal evolution. From a methodological aspect, "conservation" mainly considers genes or traits which species have in common, while "derivedness" additionally covers those that are not commonly shared, such as novel or lost traits and genes to evaluate changes from the time of divergence from a common ancestor. Due to these differences, while conservation-oriented methods are effective in identifying ancestral features, they may be prone to underestimating the overall changes accumulated during the evolution of certain lineages. Herein, we describe our recently developed method, "transcriptomic derivedness index", for estimating the phenotypic derivedness of embryos with a molecular approach using the whole-embryonic transcriptome as a phenotype. Although echinoderms are often considered as highly derived species, our analyses with this method showed that their embryos, at least at the transcriptomic level, may not be much more derived than those of chordates. We anticipate that the future development of derivedness-oriented methods could provide quantitative indicators for finding highly/lowly evolvable traits.

  6. Beyond recapitulation: Past, present, and future. International-journal Invited Peer-reviewed

    Masahiro Uesaka, Naoki Irie

    Journal of experimental zoology. Part B, Molecular and developmental evolution　338　(1-2)　9-12　2022/01

    DOI： 10.1002/jez.b.23116 　

  7. Derivedness Index for Estimating Degree of Phenotypic Evolution of Embryos: A Study of Comparative Transcriptomic Analyses of Chordates and Echinoderms Peer-reviewed

    Jason Cheok Kuan Leong, Yongxin Li, Masahiro Uesaka, Yui Uchida, Akihito Omori, Meng Hao, Wenting Wan, Yang Dong, Yandong Ren, Si Zhang, Tao Zeng, Fayou Wang, Luonan Chen, Gary Wessel, Brian T. Livingston, Cynthia Bradham, Wen Wang, Naoki Irie

    Frontiers in Cell and Developmental Biology　9　2021/11/26

    Publisher: Frontiers Media SA

    DOI： 10.3389/fcell.2021.749963 　

    eISSN： 2296-634X

    More details Close

    Species retaining ancestral features, such as species called living fossils, are often regarded as less derived than their sister groups, but such discussions are usually based on qualitative enumeration of conserved traits. This approach creates a major barrier, especially when quantifying the degree of phenotypic evolution or degree of derivedness, since it focuses only on commonly shared traits, and newly acquired or lost traits are often overlooked. To provide a potential solution to this problem, especially for inter-species comparison of gene expression profiles, we propose a new method named “derivedness index” to quantify the degree of derivedness. In contrast to the conservation-based approach, which deals with expressions of commonly shared genes among species being compared, the derivedness index also considers those that were potentially lost or duplicated during evolution. By applying our method, we found that the gene expression profiles of penta-radial phases in echinoderm tended to be more highly derived than those of the bilateral phase. However, our results suggest that echinoderms may not have experienced much larger modifications to their developmental systems than chordates, at least at the transcriptomic level. In vertebrates, we found that the mid-embryonic and organogenesis stages were generally less derived than the earlier or later stages, indicating that the conserved phylotypic period is also less derived. We also found genes that potentially explain less derivedness, such as Hox genes. Finally, we highlight technical concerns that may influence the measured transcriptomic derivedness, such as read depth and library preparation protocols, for further improvement of our method through future studies. We anticipate that this index will serve as a quantitative guide in the search for constrained developmental phases or processes.

  8. MeCP2 controls neural stem cell fate specification through miR-199a-mediated inhibition of BMP-Smad signaling International-journal Peer-reviewed

    Hideyuki Nakashima, Keita Tsujimura, Koichiro Irie, Takuya Imamura, Cleber A. Trujillo, Masataka Ishizu, Masahiro Uesaka, Miao Pan, Hirofumi Noguchi, Kanako Okada, Kei Aoyagi, Tomoko Andoh-Noda, Hideyuki Okano, Alysson R. Muotri, Kinichi Nakashima

    Cell Reports　35　(7)　109124-109124　2021/05

    Publisher: Elsevier BV

    DOI： 10.1016/j.celrep.2021.109124 　

    ISSN： 2211-1247

    More details Close

    Rett syndrome (RTT) is a severe neurological disorder, with impaired brain development caused by mutations in MECP2; however, the underlying mechanism remains elusive. We know from previous work that MeCP2 facilitates the processing of a specific microRNA, miR-199a, by associating with the Drosha complex to regulate neuronal functions. Here, we show that the MeCP2/miR-199a axis regulates neural stem/precursor cell (NS/PC) differentiation. A shift occurs from neuronal to astrocytic differentiation of MeCP2- and miR-199a-deficient NS/PCs due to the upregulation of a miR-199a target, Smad1, a downstream transcription factor of bone morphogenetic protein (BMP) signaling. Moreover, miR-199a expression and treatment with BMP inhibitors rectify the differentiation of RTT patient-derived NS/PCs and development of brain organoids, respectively, suggesting that facilitation of BMP signaling accounts for the impaired RTT brain development. Our study illuminates the molecular pathology of RTT and reveals the MeCP2/miR-199a/Smad1 axis as a potential therapeutic target for RTT.

  9. Erratum: Author Correction: Genomic insights of body plan transitions from bilateral to pentameral symmetry in Echinoderms (Communications biology (2020) 3 1 (371))

    Yongxin Li, Akihito Omori, Rachel L. Flores, Sheri Satterfield, Christine Nguyen, Tatsuya Ota, Toko Tsurugaya, Tetsuro Ikuta, Kazuho Ikeo, Mani Kikuchi, Jason C K Leong, Adrian Reich, Meng Hao, Wenting Wan, Yang Dong, Yaondong Ren, Si Zhang, Tao Zeng, Masahiro Uesaka, Yui Uchida, Xueyan Li, Tomoko F. Shibata, Takahiro Bino, Kota Ogawa, Shuji Shigenobu, Mariko Kondo, Fayou Wang, Luonan Chen, Gary Wessel, Hidetoshi Saiga, R Andrew Cameron, Brian Livingston, Cynthia Bradham, Wen Wang, Naoki Irie

    Communications biology　4　(1)　459　2021/04/06

    Publisher: NLM (Medline)

    DOI： 10.1038/s42003-021-02005-4 　

    ISSN： 2399-3642

  10. The developmental hourglass model and recapitulation: An attempt to integrate the two models International-journal Invited Peer-reviewed

    Masahiro Uesaka, Shigeru Kuratani, Naoki Irie

    Journal of Experimental Zoology Part B: Molecular and Developmental Evolution　338　(1-2)　76-86　2021/01/27

    DOI： 10.1002/jez.b.23027 　

    More details Close

    Recapitulation is a hypothetical concept that assumes embryogenesis of an animal parallels its own phylogenetic history, sequentially developing from more ancestral features to more derived ones. This concept predicts that the earliest developmental stage of various animals should represent the most evolutionarily conserved patterns. Recent transcriptome-based studies, on the other hand, have reported that mid-embryonic, organogenetic periods show the highest level of conservation (the developmental hourglass model). This, however, does not rule out the possibility that recapitulation would still be detected after the mid-embryonic period. In accordance with this, recapitulation-like morphological features are enriched in late developmental stages. Moreover, our recent chromatin accessibility-based study provided molecular evidence for recapitulation in the mid-to-late embryogenesis of vertebrates, as newly evolved gene regulatory elements tended to be activated at late embryonic stages. In this review, we revisit the recapitulation hypothesis, together with recent molecular-based studies that support the developmental hourglass model. We contend that the recapitulation hypothesis does not entirely contradict the developmental hourglass model and that these two may even coexist in later embryonic stages of vertebrates. Finally, we review possible mechanisms underlying the recapitulation pattern of chromatin accessibility together with the hourglass-like evolutionary conservation in vertebrate embryogenesis.

  11. How can recapitulation be reconciled with modern concepts of evolution? International-journal Invited Peer-reviewed

    Shigeru Kuratani, Masahiro Uesaka, Naoki Irie

    Journal of Experimental Zoology Part B: Molecular and Developmental Evolution　338　(1-2)　28-35　2020/12/31

    DOI： 10.1002/jez.b.23020 　

    More details Close

    To understand Haeckel's idea of recapitulation with modern evolutionary biology, one has to realize how evolutionarily conserved embryonic stages appear sequentially in developmental processes as chains of causality. Whether the idea of evolution was accepted or not, Haeckel and von Baer commonly saw an importance of a particularly conserved mid-embryonic stage in biphasic development of metazoans, the phylotype, that defines an animal phylum as the developmental source of a basic body plan. In an evolutionary context, the phylotypic stage was once understood by Haeckel to reflect the common ancestor of animal phyla, which went through hypermorphosis independently into various phyla. Recent comprehensive molecular studies, however, accumulated data to refute this idea. The conserved embryonic pattern does not reflect an ancestral adult morphology but appears to have arisen primarily as an embodiment of developmental constraints established through evolutionary processes. How the developmental burden results in a nested series of constraints will solve the recapitulative tendency of developmental programs.

  12. Genomic insights of body plan transitions from bilateral to pentameral symmetry in Echinoderms Peer-reviewed

    Yongxin Li, Akihito Omori, Rachel L. Flores, Sheri Satterfield, Christine Nguyen, Tatsuya Ota, Toko Tsurugaya, Tetsuro Ikuta, Kazuho Ikeo, Mani Kikuchi, Jason C. K. Leong, Adrian Reich, Meng Hao, Wenting Wan, Yang Dong, Yaondong Ren, Si Zhang, Tao Zeng, Masahiro Uesaka, Yui Uchida, Xueyan Li, Tomoko F. Shibata, Takahiro Bino, Kota Ogawa, Shuji Shigenobu, Mariko Kondo, Fayou Wang, Luonan Chen, Gary Wessel, Hidetoshi Saiga, R. Andrew Cameron, Brian Livingston, Cynthia Bradham, Wen Wang, Naoki Irie

    Communications Biology　3　(1)　2020/12

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s42003-020-1091-1 　

    eISSN： 2399-3642

  13. Recapitulation-like developmental transitions of chromatin accessibility in vertebrates International-journal Peer-reviewed

    Masahiro Uesaka, Shigeru Kuratani, Hiroyuki Takeda, Naoki Irie

    Zoological Letters　5　(1)　33-33　2019/12

    Publisher: Springer Science and Business Media {LLC}

    DOI： 10.1186/s40851-019-0148-9 　

    More details Close

    The relationship between development and evolution has been a central theme in evolutionary developmental biology. Across the vertebrates, the most highly conserved gene expression profiles are found at mid-embryonic, organogenesis stages, whereas those at earlier and later stages are more diverged. This hourglass-like pattern of divergence does not necessarily rule out the possibility that gene expression profiles that are more evolutionarily derived appear at later stages of development; however, no molecular-level evidence of such a phenomenon has been reported. To address this issue, we compared putative gene regulatory elements among different species within a phylum. We made a genome-wide assessment of accessible chromatin regions throughout embryogenesis in three vertebrate species (mouse, chicken, and medaka) and estimated the evolutionary ages of these regions to define their evolutionary origins on the phylogenetic tree. In all the three species, we found that genomic regions tend to become accessible in an order that parallels their phylogenetic history, with evolutionarily newer gene regulations activated at later developmental stages. This tendency was restricted only after the mid-embryonic, phylotypic periods. Our results imply a phylogenetic hierarchy of putative regulatory regions, in which their activation parallels the phylogenetic order of their appearance. One evolutionary mechanism that may explain this phenomenon is that newly introduced regulatory elements are more likely to survive if activated at later stages of embryogenesis. Possible relationships between this phenomenon and the so-called recapitulation are discussed.

  14. Embryonic lethality is not sufficient to explain hourglass-like conservation of vertebrate embryos Peer-reviewed

    Yui Uchida, Masahiro Uesaka, Takayoshi Yamamoto, Hiroyuki Takeda, Naoki Irie

    EvoDevo　9　(1)　2018/03/16

    Publisher: BioMed Central Ltd.

    DOI： 10.1186/s13227-018-0095-0 　

    ISSN： 2041-9139

  15. Constrained vertebrate evolution by pleiotropic genes/631/181/2806/631/553/2716 article Peer-reviewed

    Haiyang Hu, Masahiro Uesaka, Song Guo, Kotaro Shimai, Tsai-Ming Lu, Fang Li, Satoko Fujimoto, Masato Ishikawa, Shiping Liu, Yohei Sasagawa, Guojie Zhang, Shigeru Kuratani, Jr-Kai Yu, Takehiro G. Kusakabe, Philipp Khaitovich, Naoki Irie

    Nature Ecology and Evolution　1　(11)　1722-1730　2017/11/01

    Publisher: Nature Publishing Group

    DOI： 10.1038/s41559-017-0318-0 　

    ISSN： 2397-334X

  16. Evolutionary acquisition of promoter-associated non-coding RNA (pancRNA) repertoires diversifies species-dependent gene activation mechanisms in mammals. International-journal Peer-reviewed

    Masahiro Uesaka, Kiyokazu Agata, Takao Oishi, Kinichi Nakashima, Takuya Imamura

    BMC genomics　18　(1)　285-285　2017/04/07

    Publisher: Springer Nature

    DOI： 10.1186/s12864-017-3662-1 　

    ISSN： 1471-2164

    More details Close

    BACKGROUND: Recent transcriptome analyses have shown that long non-coding RNAs (ncRNAs) play extensive roles in transcriptional regulation. In particular, we have reported that promoter-associated ncRNAs (pancRNAs) activate the partner gene expression via local epigenetic changes. RESULTS: Here, we identify thousands of genes under pancRNA-mediated transcriptional activation in five mammalian species in common. In the mouse, 1) pancRNA-partnered genes confined their expression pattern to certain tissues compared to pancRNA-lacking genes, 2) expression of pancRNAs was significantly correlated with the enrichment of active chromatin marks, H3K4 trimethylation and H3K27 acetylation, at the promoter regions of the partner genes, 3) H3K4me1 marked the pancRNA-partnered genes regardless of their expression level, and 4) C- or G-skewed motifs were exclusively overrepresented between-200 and-1 bp relative to the transcription start sites of the pancRNA-partnered genes. More importantly, the comparative transcriptome analysis among five different mammalian species using a total of 25 counterpart tissues showed that the overall pancRNA expression profile exhibited extremely high species-specificity compared to that of total mRNA, suggesting that interspecies difference in pancRNA repertoires might lead to the diversification of mRNA expression profiles. CONCLUSIONS: The present study raises the interesting possibility that the gain and/or loss of gene-activation-associated pancRNA repertoires, caused by formation or disruption of the genomic GC-skewed structure in the course of evolution, finely shape the tissue-specific pattern of gene expression according to a given species.

  17. miR-199a Links MeCP2 with mTOR Signaling and Its Dysregulation Leads to Rett Syndrome Phenotypes. International-journal Peer-reviewed

    Keita Tsujimura, Koichiro Irie, Hideyuki Nakashima, Yoshihiro Egashira, Yoichiro Fukao, Masayuki Fujiwara, Masayuki Itoh, Masahiro Uesaka, Takuya Imamura, Yasukazu Nakahata, Yui Yamashita, Takaya Abe, Shigeo Takamori, Kinichi Nakashima

    Cell reports　12　(11)　1887-901　2015/09/22

    Publisher: Elsevier {BV}

    DOI： 10.1016/j.celrep.2015.08.028 　

    ISSN： 2211-1247

    More details Close

    Rett syndrome (RTT) is a neurodevelopmental disorder caused by MECP2 mutations. Although emerging evidence suggests that MeCP2 deficiency is associated with dysregulation of mechanistic target of rapamycin (mTOR), which functions as a hub for various signaling pathways, the mechanism underlying this association and the molecular pathophysiology of RTT remain elusive. We show here that MeCP2 promotes the posttranscriptional processing of particular microRNAs (miRNAs) as a component of the microprocessor Drosha complex. Among the MeCP2-regulated miRNAs, we found that miR-199a positively controls mTOR signaling by targeting inhibitors for mTOR signaling. miR-199a and its targets have opposite effects on mTOR activity, ameliorating and inducing RTT neuronal phenotypes, respectively. Furthermore, genetic deletion of miR-199a-2 led to a reduction of mTOR activity in the brain and recapitulated numerous RTT phenotypes in mice. Together, these findings establish miR-199a as a critical downstream target of MeCP2 in RTT pathogenesis by linking MeCP2 with mTOR signaling.

  18. Gene activation-associated long noncoding RNAs function in mouse preimplantation development. International-journal Peer-reviewed

    Nobuhiko Hamazaki, Masahiro Uesaka, Kinichi Nakashima, Kiyokazu Agata, Takuya Imamura

    Development (Cambridge, England)　142　(5)　910-20　2015/03/01

    Publisher: The Company of Biologists

    DOI： 10.1242/dev.116996 　

    ISSN： 0950-1991

    More details Close

    In mice, zygotic activation occurs for a wide variety of genes, mainly at the 2-cell stage. Long noncoding RNAs (lncRNAs) are increasingly being recognized as modulators of gene expression. In this study, directional RNA-seq of MII oocytes and 2-cell embryos identified more than 1000 divergently transcribed lncRNA/mRNA gene pairs. Expression of these bidirectional promoter-associated noncoding RNAs (pancRNAs) was strongly associated with the upregulation of their cognate genes. Conversely, knockdown of three abundant pancRNAs led to reduced mRNA expression, accompanied by sustained DNA methylation even in the presence of enzymes responsible for DNA demethylation. In particular, microinjection of siRNA against the abundant pancRNA partner of interleukin 17d (Il17d) mRNA at the 1-cell stage caused embryonic lethality, which was rescued by supplying IL17D protein in vitro at the 4-cell stage. Thus, this novel class of lncRNAs can modulate the transcription machinery in cis to activate zygotic genes and is important for preimplantation development.

  19. Roles of Epigenetics in the Neural Stem Cell and Neuron Peer-reviewed

    Naoki Yamamoto, Masahiro Uesaka, Takuya Imamura, Kinichi Nakashima

    Epigenetics in Psychiatry　51-78　2014/06/20

    Publisher: Elsevier Inc.

    DOI： 10.1016/B978-0-12-417114-5.00004-8 　

  20. Bidirectional promoters are the major source of gene activation-associated non-coding RNAs in mammals. International-journal Peer-reviewed

    Masahiro Uesaka, Osamu Nishimura, Yasuhiro Go, Kinichi Nakashima, Kiyokazu Agata, Takuya Imamura

    BMC genomics　15　(1)　35-35　2014/01/17

    Publisher: Springer Nature

    DOI： 10.1186/1471-2164-15-35 　

    ISSN： 1471-2164

    More details Close

    BACKGROUND: The majority of non-coding RNAs (ncRNAs) involved in mRNA metabolism in mammals have been believed to downregulate the corresponding mRNA expression level in a pre- or post-transcriptional manner by forming short or long ncRNA-mRNA duplex structures. Information on non-duplex-forming long ncRNAs is now also rapidly accumulating. To examine the directional properties of transcription at the whole-genome level, we performed directional RNA-seq analysis of mouse and chimpanzee tissue samples. RESULTS: We found that there is only about 1% of the genome where both the top and bottom strands are utilized for transcription, suggesting that RNA-RNA duplexes are not abundantly formed. Focusing on transcription start sites (TSSs) of protein-coding genes revealed that a significant fraction of them contain switching-points that separate antisense- and sense-biased transcription, suggesting that head-to-head transcription is more prevalent than previously thought. More than 90% of head-to-head type promoters contain CpG islands. Moreover, CCG and CGG repeats are significantly enriched in the upstream regions and downstream regions, respectively, of TSSs located in head-to-head type promoters. Genes with tissue-specific promoter-associated ncRNAs (pancRNAs) show a positive correlation between the expression of their pancRNA and mRNA, which is in accord with the proposed role of pancRNA in facultative gene activation, whereas genes with constitutive expression generally lack pancRNAs. CONCLUSIONS: We propose that single-stranded ncRNA resulting from head-to-head transcription at GC-rich sequences regulates tissue-specific gene expression.

  21. Epigenetic setting and reprogramming for neural cell fate determination and differentiation Peer-reviewed

    Takuya Imamura, Masahiro Uesaka, Kinichi Nakashima

    Philosophical Transactions of the Royal Society B: Biological Sciences　369　(1652)　20130511-20130511　2014

    Publisher: Royal Society of London

    DOI： 10.1098/rstb.2013.0511 　

    ISSN： 1471-2970 0962-8436

  22. Cell - to Species-Level Diversity of Epigenetic Setting for Androgen Receptor Expression in Mammals Peer-reviewed

    Masahiro Uesaka, Takuya Imamura

    Journal of Steroids & Hormonal Science　01　(S2)　2012

    Publisher: {OMICS} Publishing Group

    DOI： 10.4172/2157-7536.s2-004 　

    ISSN： 2157-7536

  23. Single-stranded noncoding RNAs mediate local epigenetic alterations at gene promoters in rat cell lines Peer-reviewed

    Junko Tomikawa, Hiroko Shimokawa, Masahiro Uesaka, Naoki Yamamoto, Yuji Mori, Hiroko Tsukamura, Kei-Ichiro Maeda, Takuya Imamura

    Journal of Biological Chemistry　286　(40)　34788-34799　2011/10/07

    Publisher: American Society for Biochemistry {\&} Molecular Biology ({ASBMB})

    DOI： 10.1074/jbc.M111.275750 　

    ISSN： 0021-9258 1083-351X

    eISSN： 1083-351X

Show all ︎Show first 5

Misc. 16

  1. 円口類ヌタウナギと脊椎動物初期進化における全ゲノム重複 Invited

    上坂将弘, 菅原文昭, 倉谷滋, PASCUAL-ANAYA Juan

    生物の科学 遺伝　78　(4)　2024/07

    ISSN： 0387-0022

  2. In the Spotlight–Postdoc Invited

    Masahiro Uesaka

    Journal of Experimental Zoology Part B: Molecular and Developmental Evolution　2020/09/17

    Publisher: Wiley

    DOI： 10.1002/jez.b.23003 　

  3. Identification and analysis of tetrapod-specific conserved genome sequences related to limb development

    工藤栄大, 上坂将弘, 牧野能士, 田村宏治

    日本分子生物学会年会プログラム・要旨集(Web)　46th　2023

  4. Cell behavior during the developmental event of pectoral fin-specific structure

    岡山舜, 上坂将弘, 阿部玄武, 森下喜弘, 田村宏治

    日本分子生物学会年会プログラム・要旨集(Web)　46th　2023

  5. Observation of muscle regenerative ability in the zebrafish pectoral-fin endoskeletal region

    横山幹恭, 上坂将弘, 吉田渓悟, 田村宏治

    日本分子生物学会年会プログラム・要旨集(Web)　46th　2023

  6. 動物の解剖学的基本パターンはなぜ進化的に保守的なのか

    入江直樹, 入江直樹, HU Haiyan, 内田唯, 上坂将弘, WANG Wen, WANG Wen, KHAITOVICH Philipp, BRADHAM Cynthia

    日本解剖学会総会・全国学術集会抄録集(CD-ROM)　127th　2022

  7. What are the potential mechanisms behind phylogenetic inertia observed for the evolution of animal bodyplan?

    入江直樹, 入江直樹, HU Haiyan, 内田唯, 内田唯, 上坂将弘, BRADHAM Cynthia, 倉谷滋, KHAITOVICH Philipp

    日本進化学会大会プログラム・講演要旨集(Web)　22nd　2020

  8. 遺伝子の使い回しは進化的多様化にとって諸刃の剣か

    入江直樹, 内田唯, 上坂将弘, 倉谷滋, YU Jr-Kai, ZHANG Guojie, 日下部岳広, PHILIPP Khaitovich

    日本分子生物学会年会プログラム・要旨集(Web)　42nd　2019

  9. 脊椎動物発生のオープンクロマチン動態に見られた系統進化の反復的パターン

    上坂将弘, 倉谷滋, 武田洋幸, 入江直樹

    日本分子生物学会年会プログラム・要旨集(Web)　42nd　2019

  10. 脊椎動物の発生過程は進化を反復するのか?

    上坂将弘, 倉谷滋, 武田洋幸, 入江直樹

    日本進化学会大会プログラム・講演要旨集(Web)　21st　2019

  11. 多面発現遺伝子が進化的拘束をもたらすメカニズム

    長倉和也, 上坂将弘, 入江直樹

    日本進化学会大会プログラム・講演要旨集(Web)　21st　2019

  12. 表現型ゆらぎは脊椎動物発生中期の保存性に寄与しうるか?

    内田唯, 上坂将弘, 武田洋幸, 武田洋幸, 入江直樹, 入江直樹

    日本分子生物学会年会プログラム・要旨集(Web)　41st　2018

  13. なぜ動物ボディプラン進化は保守的なのか

    HU Haiyang, GUO Song, 上坂将弘, 内田唯, 島井光太郎, LU Tsai-Ming, LI Fang, 藤本聡子, 石川雅人, LIU Shiping, 笹川洋平, ZHANG Guojie, ZHANG Guojie, 倉谷滋, YU Jr-Kai, 日下部岳広, KHAITOVICH Philipp, 入江直樹

    日本進化学会大会プログラム・講演要旨集(Web)　18th　2016

  14. マカクザル特異的偽遺伝子挿入に由来する非コードRNAによる遺伝子プロモーターのDNA脱メチル化

    上坂将弘, 西村理, 西村理, 大石高生, 今井啓雄, 阿形清和, 今村拓也

    日本分子生物学会年会プログラム・要旨集(Web)　35th　2012

  15. マカクザルにおける偽遺伝子由来promoter-associated noncoding RNA(pancRNA)による種特異的転写活性化

    上坂将弘, 西村理, 大石高生, 今井啓雄, 阿形清和, 今村拓也

    Journal of Reproduction and Development　57　(Suppl Japanese Issue)　2011

    ISSN： 0916-8818

  16. マウス・サル脳における種特異的promoter‐associated noncoding RNAの同定

    上坂将弘, 上田泰己, 宇野健一郎, 阿形清和, 今村拓也

    Journal of Reproduction and Development　55　(Supplement)　J91　2009/08/25

    DOI： 10.14882/jrds.102.0.209.0 　

    ISSN： 0916-8818

Show all ︎Show first 5

Presentations 12

  1. Towards understanding the evolutionary trajectories of gene regulatory landscapes and forelimb morphology in the Galloanserae lineage Invited

    Masahiro Uesaka

    The 4th AsiaEvo　2025/12/11

  2. The developmental hourglass model and the vertebrate body plan conservation: insights from single-cell level transcriptome analysis

    Masahiro Uesaka

    2023/12

  3. 比較オミクス解析から迫る個体発生と進化の関係性 Invited

    上坂 将弘

    NGS EXPO　2023/11

  4. Does vertebrate embryogenesis recapitulate its evolutionary history?

    Masahiro Uesaka

    The 2nd AsiaEvo Conference　2021/08

  5. Testing the recapitulative pattern in vertebrate embryogenesis from the perspective of gene regulation Invited

    Masahiro Uesaka

    JSDB Online Trial Meeting 2020　2020/09

  6. 脊椎動物発生のオープンクロマチン動態に見られた系統進化の反復的パターン

    上坂 将弘

    第42回 日本分子生物学会年会　2019/11

  7. 脊椎動物の胚発生における反復説の検証 Invited

    上坂 将弘

    日本動物学会第90回大阪大会　2019/09

  8. 脊椎動物の発生過程は進化を反復するのか？ Invited

    上坂 将弘

    日本進化学会第21回大会　2019/08

  9. Species-specific pseudogene insertions generate cis-acting RNA for promoter demethylation in the macaque.

    2012/12

  10. マカクザルにおける偽遺伝子由来promoter-associated noncoding RNA (pancRNA) による種特異的転写活性化

    上坂 将弘

    第104回 日本繁殖生物学会大会　2011/09

  11. マウス・サル脳における種特異的promoter-associated noncoding RNAの同定

    上坂 将弘

    RNAフロンティアミーティング2010　2010/09

  12. マウス・サル脳における種特異的promoter-associated noncoding RNAの同定

    上坂 将弘

    第102回 日本繁殖生物学会大会　2009/08

Show all Show first 5

Research Projects 7

  1. 遺伝子発現制御予測から迫る形態進化可能性の変遷

    上坂 将弘

    Offer Organization: 科学技術振興機構

    Category: 戦略的な研究開発の推進/創発的研究支援事業

    2025 - 2032

    More details Close

    生物が進化するポテンシャル（進化可能性）は、生物多様性の変遷を理解する上で重要な概念ですが、多細胞動物では定量的検証が難しく、進化学のフロンティアの一つとなっています。本研究は真骨魚類をモデルとし、形態形成を駆動する遺伝子発現制御を深層学習により予測し、ゲノム情報の変化に応じて遺伝子発現制御と形態がどのように変わるかを定量します。さらに、実験的検証を通し、進化可能性の進化の一般則を明らかにします。

  2. 脊椎動物器官発生における遺伝子制御活性解析による進化と発生の反復傾向の実体解明

    上坂 将弘

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 若手研究

    Category: 若手研究

    Institution: 国立研究開発法人理化学研究所

    2022/04/01 - 2025/03/31

  3. 棘皮動物バフンウニの後期発生における遺伝子発現制御の反復傾向検証

    Offer Organization: 水産無脊椎動物研究所

    System: 個別研究助成課題

    2023/04 -

  4. 脊索動物胚発生の分子発生システムゆらぎ測定と進化的保存性

    入江 直樹, 上坂 将弘

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 新学術領域研究(研究領域提案型)

    Category: 新学術領域研究(研究領域提案型)

    Institution: 東京大学

    2017/06/30 - 2022/03/31

    More details Close

    個体発生と系統発生の関係性として、従来は、発生の最初期が最も祖先的であるだろうという仮説が漠然と信じられてきた。von Baerの発生第三法則やヘッケルの反復説などにルーツを持つ仮説である。近年の研究ではこれらの仮説は支持されず、「発生の途中段階（特に器官形成期）」が強固に保存されているとする発生砂時計モデルが支持されている。 一方で、なぜ「発生の途中段階」がこのように限られた多様性しか示さないのかについては、自然淘汰や中立説などの従来の進化理論では十分な説明ができておらず、その進化メカニズムも不明のままである。それが解明されれば、「ボディプラン」と呼ばれる解剖学的特徴が数億年以上にわたって変化してこなかったという進化的事実が説明される可能性があり、さらには、進化学に「進化の方向性や制約」という新たな視点を加えることができると期待できる。本課題では、器官形成期が保存される仕組みだけでなく、発生の初期や後期が多様化した仕組みについても解明を目指している。今年度は、器官形成期以降に生じる遺伝子制御配列(ATACseqにより推定)の進化的傾向について脊椎動物を対象に探ってみたところ、発生の遅い時期ほど進化的に新しい制御領域を用いているという法則性がみえてきた(Uesaka et al. bioRxiv 481309)。これは、von Baerの発生第三法則と砂時計モデルの融合型モデルとも言え、器官形成期以降に多様化する際にも何かしらの制約がある可能性を意味している。器官形成期はこうした制御領域多様化法則の開始点である可能性もあり、今後さらなる研究が期待される。加えて、器官形成期に生じる揺らぎの測定に関しても順調に実験系構築・技術基盤構築を進めており、すでに揺らぎ応答進化理論との整合性の検証が目前となっている。

  5. Testing the recapitulation tendency in vertebrate embryogenesis by analyzing developmental patterns of gene regulatory activities

    Masahiro Uesaka

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Early-Career Scientists

    Institution: Institute of Physical and Chemical Research

    2018/04/01 - 2021/03/31

    More details Close

    Animal development generally proceeds from a single-celled zygote to a complex multicellular organism. This has led biologists to propose parallel relationships between development and evolution. One of the famous hypotheses is recapitulation theory. This assumes embryogenesis of an animal parallels its evolutionary history, sequentially developing from more ancestral features to more derived ones. However, no molecular studies have not quantitatively supported such recapitulation in vertebrate embryogenesis so far. In this study, we tested the recapitulation from the perspective of gene regulation. By examining developmental changes in active gene regulatory regions and estimating their evolutionary ages, we found that regulatory regions tend to become sequentially activated in an order that parallels their evolutionary ages in three vertebrates. This suggests a recapitulative pattern in gene regulatory activity during embryogenesis.

  6. 終脳発生の進化的多様性の起源解明に向けた比較オミックス解析

    上坂 将弘

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 特別研究員奨励費

    Category: 特別研究員奨励費

    Institution: 東京大学

    2015/04/24 - 2018/03/31

    More details Close

    生物の様々な行動を司る終脳の発生は、各系統に特徴的な形態と脳機能が密接に関わり合いながら進行する。脊椎動物の終脳の進化に関しては比較形態学的知見が蓄積されてきた一方で、こうした終脳形態の多様性に対応する発生プログラムと、その進化的変化は殆どわかっていない。本研究は、脊椎動物進化の過程で獲得されてきたゲノム配列がどのように現生生物種の発生プログラムにおいて機能しているかを調べることを目的とし、解析を進めた。 本年度は、これまでに収集した遺伝子発現プロファイル、オープンクロマチンプロファイルとゲノム比較情報を統合し解析を進めた。まず、マウスの終脳の遺伝子発現プロファイルを用いて、終脳の発生プログラムが進化的にどの程度変化してきたかを調べた。その結果、終脳発生における遺伝子発現プロファイルは発生の進行に従って進化的に新しい遺伝子が増加していく傾向が見られた。この傾向は、咽頭胚期以降の発生過程において全胚由来の遺伝子発現プロファイルは多様化していくという知見と一致する。また、終脳と胚全体の遺伝子発現プロファイルを比較したところ、遺伝子の獲得と喪失の観点からすれば、終脳の発生プログラムは進化的に比較的古い遺伝子からなること示唆された。 脊椎動物の進化において変化が生じたゲノム領域は、遺伝子外領域が多くを占めることが明らかになってきた。そこで、終脳発生プログラムにおいて活性化される遺伝子制御領域を調べるために、終脳発生と全胚発生のATAC-seqデータを解析した。どちらのデータにおいても、殆どのオープンクロマチン領域が、脊椎動物以降の進化の過程で獲得されたものであった。 以上の遺伝子や遺伝子制御領域のゲノム進化に着目した解析結果から、脊椎動物進化において終脳の発生プログラムは器官発生の初期ほど変化してこなかったと考えられ、また終脳の発生プログラムは進化的に古い可能性が示唆された。

  7. 偽遺伝子挿入による種特異的非コードＲＮＡ獲得に基づく哺乳類エピゲノム進化

    上坂 将弘

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 特別研究員奨励費

    Category: 特別研究員奨励費

    Institution: 京都大学

    2012/04/01 - 2015/03/31

    More details Close

    本課題では、長鎖非コードRNAがもたらす生物種間多様性の理解を目指し、配列特異的なエピジェネティック制御に関わる長鎖非コードRNA、promoter-associated ncRNA (pancRNA)に着目し、pancRNAによる遺伝子発現制御の普遍的特徴とpancRNAのレパートリーの生物種間多様性の解明を目的としている。哺乳類に属する生物種はほぼ共通の遺伝子セットを持っているにも関わらず、形態や細胞組成など様々な点において、多様性が見られる。共通の遺伝子セットから生み出される多様性は、遺伝子発現制御の違いによるものと考えられており、特に昨今、遺伝子発現制御における長鎖非コードRNAの重要性が強調されている。 本課題において、哺乳類5種・5組織のトランスクリプトーム解析から、pancRNAがゲノムワイドに存在することを示した。pancRNAによる発現制御を受ける遺伝子は、遺伝子発現パターン、エピジェネティック修飾、ゲノム配列において共通の特徴を持つ傾向があることを示した。また、比較トランスクリプトーム解析から、pancRNAは相同な組織間であっても遺伝子発現プロファイルに生物種間多様性がみられることがわかった。これは生物種間で遺伝子発現パターンが異なるpancRNAが多く存在していることを示唆している。 本研究より、生物種ごとに数千のpancRNAを同定できた。その中から、生物種特異的pancRNAを持つ遺伝子を抽出し、遺伝子発現パターンとプロモーター領域の配列を、そのオーソログ遺伝子同士で比較した。その結果、「シトシンまたはグアニンがプロモーター領域に多くなるような変異が、pancRNAの発現獲得に繋がり、このpancRNAの発現がタンパクコード遺伝子の発現の組織特異性の上昇につながった」、ということが示唆された。

Show all Show first 5