Research

Takeda Lab's Educational/Research Policy

Zebrafish 20-hour embryo, transplanted by fluorescently labeled cells

Medaka embryo at the segmentation stage (1.5 day), after dechorionation

In Takeda Lab, you can see and feel the beauty of the development process with your own eyes, formulate hypotheses based on fundamental questions and observations, verify the them through experiments, generate new questions, and gradually advance your research by repeating these processes. You are free to pursue basic research based on your own interests. In return, a high level of research quality is required, and you need to spend a lot of time reading and studying papers and doing a lot of experiments. It may be hard at first, but we help each other to make your studies and research fruitful.

Left-right asymmetry formation by secreted signaling proteins

Although vertebrates develop from apparently symmetrical fertilized eggs, there are clear left-right (LR) asymmetries in the arrangement of internal organs, such as the heart and gastrointestinal tract. How this LR asymmetry is formed during development is a fascinating question for embryologists, and the answer to this question at the molecular level remains unresolved. Our laboratory aims to discover a novel mechanism of LR asymmetry formation by visualizing and manipulating the behavior of signaling factors in the embryo that are believed to induce LR asymmetric gene expression (Ikeda et al., Dev. Growth Differ., 2023; Ikeda et al., in preparation). We also explore extracellular matrices that regulate the extracellular dynamics of signaling molecules by utilizing genome editing and cutting-edge imaging technologies.

Kupffer's vesicle in a medaka 9-somite embryo (arrowhead)

Transgenic zebrafish embryo （dand5:EGFP）whose Kupffer's vesicle cells are labelled with GFP

Left-sided expression of spaw in a zebrafish 22-somite embryo

Mechanism of otolith formation using ha mutants

The ha mutant is a natural Japanese medaka mutant that exhibits an interesting phenotype in which otoliths in the otic vesicle are not produced. A previous study in our laboratory revealed that the causative gene of the ha mutant encodes Polyketide synthase 1 (Pks1) (Hojo et al., Zool. Lett., 2015). Pks1 is an enzyme that synthesizes a group of organic compounds called polyketides, but it remains unclear how this enzyme participate in otolith formation. This is an important question not only for developmental biology, but also for the study of biomineralization process. However, the polyketide compounds produced by medaka Pks1 have not yet been identified, and furthermore, the mechanism by which Pks1 products promote otolith formation is completely unknown. In this study, we aim to identify medaka Pks1 products by biochemical approach, and to search for novel genes that cooperate with Pks1 in otolith formation by gene expression analysis in otic vesicle cells.

Evolutionary diversity of somite-derived cell types

The somite in vertebrate embryos has an interesting feature in that it gives rise to a wide variety of cell types, such as skeletal muscle and exoskeleton, at the later stages of development. We have been studying the mechanisms of segmentation of early somites and cell differentiation in post-segmented somites. In particular, a study showing that scales (a type of exoskeleton) in teleost fishes, which were previously thought to be derived from neural crest cells, originate from the somite, cast light on the evolutionary process of animal skeletal systems (Shimada et al., Nat. Commun., 2013). We now aim to compare the differentiation potential of somitic cells in various vertebrate species such as cartilaginous fishes and amniotes, using cell transplantation and single-cell transcriptome analysis.。

Epigenetic regulation of developmental genes

All cells in the vertebrate body carry the same genetic information, yet exhibit distinct characteristics depending on the tissue. During development, when undifferentiated cells differentiate into a wide variety of specialized cell types, epigenetic changes such as chromatin 3D conformation and histone modifications are thought to play a crucial role. Medaka (Oryzias latipes) is a particularly suitable model for genome and epigenome analyses, owing to its relatively small genome size of about 800 Mb (approximately one quarter that of humans). In addition, pluripotent cells can be readily obtained in large numbers from living embryos at early developmental stages. Taking advantage of these features, we are establishing genomic resources for medaka and analyzing how three-dimensional genome architecture and histone modifications in early embryos influence gene expression.

Histone modifications and gene activation

For research at the former Takeda lab, see here.

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