Cell Development, Proliferation and Death

Cells undergo a tightly regulated life cycle of growth, division and programmed death that underlies tissue development, maintenance and regeneration. In multicellular organisms, embryonic progenitors specialise through sequential induction and asymmetric division, giving rise to the gamut of differentiated cell types. Division is driven by ordered transitions through G₁, S, G₂ and M phases, controlled by cyclin–CDK complexes and checkpoint regulators that ensure DNA integrity and exact chromosome segregation. Post-mitotic cells may enter quiescence (G₀) or embark on specialised functions. Throughout life, stem cells and transit-amplifying progenitors replenish mature cell populations, while damaged or surplus cells are removed by programmed pathways. Apoptosis executes an intrinsic suicide programme via caspase-mediated proteolysis, while inflammatory caspases trigger pyroptosis, a lytic death coupled to immune signalling. The balance between proliferative and death signals is vital for tissue homeostasis; its dysregulation can lead to cancer, degenerative disorders or inflammatory disease.

Research from Nature Portfolio

High-resolution cryo-EM has revealed how cortactin stabilises Arp2/3-nucleated branches. Cortactin binds activated Arp3, bridging the Arp2/3 complex to the first actin subunit of the daughter filament and reinforcing the branch under mechanical load, thereby prolonging network lifetime and guiding cellular protrusions.

Mechanical and live-cell assays show that even without myosin activity, fibroblasts sense matrix stiffness via the viscoelasticity of flowing actin networks. Formin-driven polymerisation and Arp2/3-mediated branching mechanically reinforce the cytoskeleton, transmitting polymerisation forces to adhesions to generate substrate-dependent traction in a myosin-independent manner.

Single-molecule imaging of actin barbed ends demonstrates that formin, capping protein and twinfilin form transient ternary complexes. Twinfilin selectively displaces capping protein from these complexes, thus promoting formin-mediated elongation. This reveals how polymerases, depolymerases and cappers integrate to tune filament dynamics at the leading edge.

Cell Development, Proliferation and Death publication trend

The graph below shows the total number of articles in cell development, proliferation and death across all publications each year (not limited to Nature Index journals).

Technical terms

Actin polymerisation: Assembly of globular actin monomers into filamentous (F-actin) structures that generate force for cell shape changes and motility.

Arp2/3 complex: A seven-subunit actin nucleator that binds existing filaments and initiates branched filament formation at a characteristic 70° angle.

Caspase: A family of cysteine proteases that cleave substrates after aspartate residues to execute apoptosis and inflammatory cell death programmes.

Exosite: An auxiliary binding site on an enzyme, distinct from the catalytic active site, that enhances substrate recognition and specificity.

G₀ phase: A reversible quiescent state entered by non-dividing cells that can re-enter the cell cycle upon appropriate stimulation.

Pyroptosis: A lytic and inflammatory form of programmed cell death driven by inflammatory caspase activation of gasdermin pore formation.

References

1. Cortactin stabilizes actin branches by bridging activated Arp2/3 to its nucleated actin filament. Nature Structural & Molecular Biology (2024).
2. Myosin-independent stiffness sensing by fibroblasts is regulated by the viscoelasticity of flowing actin. Communications Materials (2024).
3. Multicomponent regulation of actin barbed end assembly by twinfilin, formin and capping protein. Nature Communications (2023).
4. Regeneration of actin filament branches from the same Arp2/3 complex. Science Advances (2024).
5. Inflammatory caspase substrate specificities. mBio (2024).
6. A Comprehensive Exploration of Caspase Detection Methods: From Classical Approaches to Cutting-Edge Innovations. International Journal of Molecular Sciences (2024).