A generalized caspase inhibitor disrupts early mammalian development

Zahra Zakeri1, Richard A Lockshin, Luis-Miguel Criado-Rodríguez

  • 1Department of Biology, Queens College and Graduate Center of the City University of New York, New York, USA. zahra_zakeri@qc.edu

Insights

Early mammalian embryo cell death is not caspase-dependent. Caspase activity plays a role in early embryos, but not in cell death, suggesting novel functions beyond apoptosis.

Area of Science:

  • Developmental Biology
  • Cell Biology
  • Mammalian Embryogenesis

Background:

  • The mechanisms of cell death in early mammalian embryos remain largely uncharacterized.
  • Understanding these processes is crucial for developmental biology and reproductive health.

Purpose of the Study:

  • To investigate the role and mechanisms of cell death in early mouse embryos.
  • To determine the involvement of caspases in embryonic cell death.

Main Methods:

  • Culturing mouse embryos in vitro from fertilization to blastula stage.
  • Utilizing caspase inhibitors, including specific inhibitors for caspases 3, 7, and 8, and a pan-caspase inhibitor (zVAD-FMK).
  • Observing and quantifying cell death events and embryonic development.

Main Results:

  • Polar body death was not inhibited by caspase inhibitors.
  • Post-cavitation cell death was unaffected by specific caspase inhibitors (3, 7, 8).
  • Pan-caspase inhibition from the 1-2 cell stage led to expanded post-cavitation death and embryo malformation/death.

Conclusions:

  • Early embryonic cell deaths in mice are not mediated by caspases.
  • Caspase activity is present and plays a role in early mammalian embryos, independent of cell death.
  • These findings suggest non-apoptotic functions for caspases during early embryogenesis.

Related Concept Videos

Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...