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Updated: Jan 14, 2026
08:55
Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
Published on: August 7, 2018
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Extrinsic apoptosis and necroptosis in telencephalic development: a single-cell mass cytometry study
Jiachen Shi1,2, Weile Liu1,2, Alison Song1
1Department of Biology, College of Arts and Sciences, University of Virginia, Charlottesville, VA, USA.
Cell Death and Differentiation
|October 21, 2025
Summary
Regulated cell death shapes the developing brain. Deleting RIPK3 and Caspase-8 increased cell count, revealing distinct roles for apoptosis and necroptosis in brain development.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Regulated cell death is crucial for brain development.
- The precise roles of extrinsic apoptosis and necroptosis in this process are not fully understood.
Purpose of the Study:
- To investigate the contributions of extrinsic apoptosis and necroptosis to telencephalon development.
- To characterize the cellular landscape of the developing mouse telencephalon in specific genetic knockout models.
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 models.
Main Results:
- Combined deletion of RIPK3 and Caspase-8 resulted in a significant 12.6% increase in total cell count.
- This finding challenges the exclusive role of intrinsic apoptosis in developmental cell elimination.
- DKO mice showed selective enrichment of Tbr2⁺ intermediate progenitors and endothelial cells, indicating cell-type-specific pathway involvement.
Conclusions:
- The study provides a revised understanding of cell number regulation during telencephalic development.
- Distinct roles for extrinsic apoptotic and necroptotic pathways were identified.
- Findings suggest potential links to neurodevelopmental disorders involving abnormal cell death.
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