Extrinsic apoptosis and necroptosis in telencephalic development: a single-cell mass cytometry study

TL;DR

The study uses single-cell mass cytometry to show that both extrinsic apoptosis and necroptosis play roles in shaping the developing mouse brain.

Contribution

The study reveals that combined deletion of RIPK3 and Caspase-8 increases cell count, challenging the idea that intrinsic apoptosis alone controls developmental cell death.

Findings

Combined deletion of RIPK3 and Caspase-8 increases total cell count by 12.6%.

DKO mice show selective enrichment of Tbr2⁺ intermediate progenitors and endothelial cells.

Extrinsic apoptosis and necroptosis have distinct, cell-type-specific roles in telencephalic development.

Abstract

Regulated cell death is integral to sculpting the developing brain, yet the relative contributions of extrinsic apoptosis and necroptosis remain unclear. Here, we leverage single-cell mass cytometry (CyTOF) to characterize the cellular landscape of the mouse telencephalon in wild-type (WT), RIPK3 knockout (RIPK3 KO), and RIPK3/Caspase-8 double knockout (DKO) mice. Strikingly, combined deletion of RIPK3 and Caspase-8 leads to a 12.6% increase in total cell count, challenging the prevailing notion that intrinsic apoptosis exclusively governs developmental cell elimination. Detailed subpopulation analysis reveals that DKO mice display selective enrichment of Tbr2⁺ intermediate progenitors and endothelial cells, underscoring distinct, cell type–specific roles for extrinsic apoptotic and necroptotic pathways. These findings provide a revised framework for understanding the coordinated regulation of cell number during telencephalic development and suggest potential mechanistic links to neurodevelopmental disorders characterized by aberrant cell death.

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