Kumiko Yoshioka-Kobayashi

Kumiko Yoshioka-Kobayashi

Researcher (Alev-G)

Position
JSPS Postdoc
Research Field
Developmental Biology

Research Overview

Live imaging-based characterization of developmental clocks

During embryonic development, a fertilized egg develops into an organism through sequential cascades of spatio-temporarily coordinated processes, such as cell division, differentiation, migration, and morphological changes. A fundamental question is how do the cells regulate when and where to trigger these events. I’ve been interested in the underlying mechanism, or developmental clocks, which control the timing and location of such processes. I have worked on analyzing the mouse segmentation clock, a molecular clock that regulates periodic somitogenesis in mice via oscillatory expression of clock genes, such as Hes7, in the presomitic mesoderm (PSM). By using the live imaging-based quantification of Hes7 expression in live mouse embryos, and in collaboration with mathematical modeling/simulation, we revealed the molecular mechanism controlling the phase synchronization of Hes7 oscillation (Yoshioka-Kobayashi et al. Nature (2020)), which is important for establishing the regular pattern of segments. In this study, we have established a novel fluorescent reporter for Hes7 based on Achilles, a yellow fluorescent protein with fast maturation kinetics (Movie 1). The reporter enabled us to quantify the clock oscillation at single cell level in live PSM tissues and to characterize Hes7 oscillation dynamics in wild type as well as mutant PSMs, which showed a desynchronization phenotype (Movie 2). I also contributed to the establishment of pluripotent stem cell-derived in vitro models of the mouse and human segmentation clocks in which Hes7 oscillation was successfully recapitulated (Matsumiya et al., Development (2018); Diaz-Cuadros et al., Nature (2020)). These models are also suitable for wide-scale studies such as drug or mutant library screening. Current key technics here to characterize the clock dynamics and somite formation are the reporter-based quantification of clock gene/morphological changes and a robust in vitro model that recapitulates key features of the segmentation clock. In the Alev Group at ASHBi, I will investigate and characterize the human segmentation clock as well as the segmentation clock of other animals by utilizing live imaging-based quantification of in vitro segmentation clocks. I will also explore the developmental clock in other cellular and tissue contexts during embryogensis in order to understand the design principles of the system, which govern spatio-temporally coordinated events during development.

Movie 1: Hes7-Achilles expression in wild type PSM explants. Confocal time-lapse imaging of mouse PSM at E10.5 carrying Hes7 Achilles reporter transgene and ROSA26-H2B-mCherry (left) and transmitted light image (right). Adapted from Yoshioka-Kobayashi et al., Nature (2020); courtesy of Springer Nature; rights reserved.

Movie 2: Hes7-Achilles expression in wild type and Lunatic fringe (Lfng)-KO PSM explants. Confocal time-lapse imaging of wild type (left) and null mutant for Lfng (right) PSM at E10.5, carrying Hes7 Achilles reporter transgene and ROSA26-H2B-mCherry. Lfng is a gene encoding a glycosyltransferase, which can modulate Delta/Notch signaling activity and is known to be important for the phase synchronization of Hes7 oscillation in the PSM. Adapted from Yoshioka-Kobayashi et al., Nature (2020); courtesy of Springer Nature; rights reserved.

Biography

Kumiko Yoshioka-Kobayashi earned her B.S. and M.S degrees in Engineering in 2010 and 2012 from Soka University, Tokyo. She then worked at the Riken Center for Developmental Biology (CDB), Kobe as a technician in the laboratory of Shin-Ichi Nishikawa. In 2013, she joined the Ryoichiro Kageyama group at the Institute for Frontier Life and Medical Sciences, Kyoto University and started her PhD work. She was a recipient of a JSPS Research Fellowship for Young Scientist (DC1) from 2014 to 2016. She obtained her PhD in 2020 from Kyoto University and then joined the Alev group at ASHBi.

Publications

Fustin JM, Ye S, Rakers C, Kaneko K, Fukumoto K, Yamano M, Versteven M, Grünewald E, Cargill SJ, Tamai TK, Xu Y, Jabbur ML, Kojima R, Lamberti ML, Yoshioka-Kobayashi K, Whitmore D, Tammam S, Howell PL, Kageyama R, Matsuo T, Stanewsky R, Golombek DA, Johnson CH, Kakeya H, van Ooijen G, Okamura H. Methylation deficiency disrupts biological rhythms from bacteria to humans. Commun Biol. 2020 May; 3(1), 211.

Yoshioka-Kobayashi K, Matsumiya M, Niino Y, Isomura A, Kori H, Miyawaki A, Kageyama R. Coupling delay controls synchronized oscillation in the segmentation clock. Nature. 2020 Apr; 580(7801), 119-123.

Diaz-Cuadros M, Wagner DE, Budjan C, Hubaud A, Tarazona OA, Donelly S, Michaut A, Al Tanoury Z, Yoshioka-Kobayashi K, Niino Y, Kageyama R, Miyawaki A, Touboul J, Pourquié O. In vitro characterization of the human segmentation clock. Nature. 2020 Apr; 580(7801), 113-118.

Takagi A, Isomura A, Yoshioka-Kobayashi K, Kageyama R. Dynamic Delta-like1 expression in presomitic mesoderm cells during somite segmentation. Gene Expression Patterns. 2020 Jan; 35, 119094.

Matsumiya M, Tomita T, Yoshioka-Kobayashi K, Isomura A, Kageyama R. ES cell-derived presomitic mesoderm-like tissues for analysis of synchronized oscillations in the segmentation clock. Development. 2018 Feb 14; 145(4), dev.156836.

Perron A, Nishikawa Y, Iwata J, Shimojo H, Takaya J, Kobayashi K, Imayoshi I, Mbenza NM, Takenoya M, Kageyama R, Kodama Y, Uesugi M. Small-molecule screening yields a compound that inhibits the cancer-associated transcription factor Hes1 via the PHB2 chaperone. J Biol Chem. 2018 May; 93(21), 8285-8294.

Kobayashi K, Ding G, Nishikawa S, Kataoka H. Role of Etv2-positive cells in the remodeling morphogenesis during vascular development. Genes Cells. 2013 Aug; 18(8), 704-721.

Awards

2015 Outstanding Oral Presentation Award at 13th International Student Seminar, Kyoto
2015 Tomy Award Outstanding Young Scientist at 22nd East Asia Joint Symposium, Okinawa
2018 Grand Prize in the category of Movies at ABIS Image Contest 2018, Yokohama

Research Group

Alev Group
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