FBS Colloquia No.374Laboratory for Embryogenesis
| Seminar or Lecture |
Fate specification triggers a positive feedback loop of TEAD–YAP and NANOG to promote epiblast formation in preimplantation embryos Naoki Hirono [Graduate Student (D4/D5), Laboratory for Embryogenesis] Bioelectric Signal Oscillation Generates the Segmentation Pattern of Zebrafish Fin Bones Toshihiro Aramaki [Assistant Professor, Laboratory for Embryogenesis] |
|---|---|
| Date and Time | 10 Dec. 2024 (Tue), 12:15～13:00 |
| Place | 2F Seminar Room, BioSystems Building |
| Language | Japanese |
| Contact |
Toshihiro Aramaki (Assistant Professor) |
Fate specification triggers a positive feedback loop of TEAD–YAP and NANOG to promote epiblast formation in preimplantation embryos
In the developmental process, the cell populations of an embryo exhibit variability in cell division, cell differentiation, and gene expression, but the embryo overcomes this variability to achieve normal development. Understanding how embryos overcome this variability and ensure normal development is one of the critical questions in developmental biology. In our laboratory, we have focused on the epiblast of mouse preimplantation embryos, which become the body, as a model that shows differentiation with variability. Differentiation into the epiblast is regulated by two systems: the segregation of NANOG and GATA6 expression and the activation of TEAD–YAP through the nuclear localization of YAP, but the relationship between these mechanisms remains unclear. We have been researching how these two mechanisms interact during epiblast differentiation to ensure normal development. In this colloquium, I introduce our research findings along with the latest results.
Bioelectric Signal Oscillation Generates the Segmentation Pattern of Zebrafish Fin Bones
Fish fins exhibit considerable diversity among species in both shape and function. Generally, they are supported by numerous long, thin bones called fin rays, each composed of multiple short bone segments. This anatomical arrangement confers both strength and high flexibility to fins, facilitating efficient thrust force generation at swimming. Extensive research with zebrafish fin mutants has shown that the segmentation pattern of fin ray bones is regulated by ion channels, including potassium channels and gap junction channels. In this study, we focus on the membrane potential of osteoblasts and express several mutant ion channels using transgenic techniques, thereby manipulating the osteoblast membrane potential. Our findings demonstrate that increasing the osteoblast membrane potential leads to a reduction in the length of individual bone segments, whereas decreasing the membrane potential results in elongated segments. These results suggest the close relationship between osteoblast membrane potential and the bone segmentation pattern. Furthermore, direct manipulation of membrane potential using channelrhodopsin-2 (ChR2), a light-gated cation channel, revealed that bone segmentation can be induced solely by elevating the osteoblast membrane potential. In single-cell RNA sequencing analysis, intriguingly, the transcriptional upregulation of a potassium channel gene, kcnq5, and a gap junction channel gene, cx43, was observed in response to the increment in osteoblast membrane potential. Loss-of-function analysis of kcnq5 or cx43 resulted in shortened bone segments (i.e., increment of segmentation), suggesting that these genes act as negative feedback regulators of repetitive segment formation. Finally, live imaging employing a calcium indicator GCaMP6s revealed locally elevated calcium signals at the tips of segmenting fin rays, providing additional evidence for a potential link between osteoblast membrane potential and bone segmentation.
