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  • Published:

How death shapes life during development

Nature Reviews Molecular Cell Biology volume 3, pages 779–787 (2002)Cite this article

Key Points

  • Programmed cell death plays a normal, formative role in developing animals.

  • Programmed cell death is involved in the formation and deletion of structures, the control of cell numbers and the elimination of abnormal cells.

  • Apoptosis and cell death with autophagy are the most common morphological forms of programmed cell death in developing animals. Apoptosis is regulated by a core cell-death machinery that involves the caspase proteases.

  • Although they are distinct, apoptosis and autophagic cell death use some common regulatory mechanisms.

  • Studies of programmed cell death have focused on the mechanisms of apoptosis and less is known about autophagic removal of cells.

  • Several factors are involved in the activation of cell death during development, including cell-lineage information, extracellular survival factors and steroid hormones.

  • The removal and degradation of dying cells during development by phagocytosis and autophagy is a crucial step downstream of the core cell-death machinery.

  • Detailed understanding of the mechanisms that regulate apoptotic and autophagic cell death will be useful in the diagnosis of abnormal cell growth and the design of rational therapies to treat human syndromes.

Abstract

The formation of an adult animal from a fertilized embryo involves the production and death of cells. Surprisingly, many cells are produced during development with an ultimate fate of death, and defects in programmed cell death can result in developmental abnormalities. Recent studies indicate that cells can die by many different mechanisms, and these differences have implications for proper animal development and disorders such as cancer and autoimmunity.

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Figure 1: Programmed cell death during development.
Figure 2: Apoptotic and autophagic cell death are regulated at distinct steps.
Figure 3: Pathways leading to programmed cell death.

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Acknowledgements

I apologize to the many researchers who were not cited in this report because of space limitations. I thank the past and present members of my laboratory, collaborators and many colleagues for helpful discussions. Studies of cell death in my laboratory are supported by NSF grant BES-9908942 and NIH grant GM59136.

Author information

Authors and Affiliations

  1. Center for Biosystems Research, University of Maryland Biotechnology Institute, College Park, Maryland, 20742, USA

    Eric H. Baehrecke

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  1. Eric H. Baehrecke
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DATABASES

Flybase

p35

SPITZ

HID

reaper

grim

sickle

EcR

usp

βFTZ-F1

BR-C

E74

E93

ark

dronc

croquemort

dcp-1

dark

Wormbase

tra-1

egl-1

CED-9

LocusLink

Bcl-2

Smac/DIABLO

XIAP

Omi/HatA2

CD36

DOCK180

Rac1

Apaf-1

caspase 3

caspase 8

caspase 9

BclX

ProSite

BH3

Glossary

BCL-2 FAMILY

Family of proteins that contain BH1–4 domains and regulate cell death.

EPISTASIS

Interaction between nonallelic genes such that the relationship within a hierarchy can be determined

NULL MUTATIONS

Mutations in genes that eliminate the protein's function.

UBIQUITIN

Polypeptide that is attached to proteins and targets them for degradation.

ECTOPIC

Event that occurs either in the wrong place or at the wrong time.

ZINC FINGER

Conserved protein domain that requires zinc nucleation to bind DNA and regulate RNA transcription.

BCL-HOMOLOGY-3 DOMAIN

Conserved domain within Bcl-2-family proteins.

TROPHIC SIGNALS

Molecules that are required for survival.

GLIA

Support cells of the nervous system.

AXON TRACTS

Group of neural-cell projections.

COMPETENCE FACTOR

Factor that enables a specific response to a stimulus at a specific location or time.

REDUNDANT

Gene or pathway that is duplicated; elimination of one therefore does not result in a defect.

SH2 AND SH3 DOMAINS

Conserved Src-homology-2 and -3 domains are found in signalling and cytoskeleton proteins, and are thought to mediate protein–protein interactions.

TRANSCRIPTOME

All of the messenger RNA species that are present in a cell, tissue or organism at a point in time.

PROTEOME

All of the protein species that are present in a cell, tissue or organism at a point in time.

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Baehrecke, E. How death shapes life during development. Nat Rev Mol Cell Biol 3, 779–787 (2002). https://doi.org/10.1038/nrm931

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