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The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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Use of LysoTracker to Detect Programmed Cell Death in Embryos and Differentiating Embryonic Stem Cells
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Extrinsic Apoptosis and Necroptosis in Telencephalic Development: A Single-Cell Mass Cytometry Study.

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    Regulated cell death sculpts the developing brain. Combined deletion of RIPK3 and Caspase-8 increased cell count, revealing distinct roles for apoptosis and necroptosis in brain development.

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    Area of Science:

    • Neuroscience
    • Developmental Biology
    • Cell Death Research

    Background:

    • Regulated cell death is crucial for brain development.
    • The specific roles of extrinsic apoptosis and necroptosis in this process are not fully understood.

    Purpose of the Study:

    • To investigate the contributions of RIPK3-mediated necroptosis and Caspase-8-mediated apoptosis to telencephalon development.
    • To characterize the cellular landscape in mice lacking these cell death pathways.

    Main Methods:

    • Single-cell mass cytometry (CyTOF) was employed.
    • Analysis was performed on wild-type (WT), RIPK3 knockout (RIPK3 KO), and RIPK3/Caspase-8 double knockout (DKO) mouse telencephalons.

    Main Results:

    • Combined deletion of RIPK3 and Caspase-8 resulted in a significant 12.6% increase in total cell count.
    • DKO mice showed selective enrichment of Tbr2⁺ intermediate progenitors and endothelial cells.
    • This challenges the idea that only intrinsic apoptosis controls developmental cell elimination.

    Conclusions:

    • Extrinsic apoptotic and necroptotic pathways have distinct, cell type-specific roles in telencephalic development.
    • These findings offer a new perspective on cell number regulation in the developing brain.
    • The study suggests potential links to neurodevelopmental disorders involving abnormal cell death.