Developmental Mechanism - Apoptosis
Introduction
This single term "apoptosis" describes the way in which the majority of cells die within our adult body are removed every day, "Programmed Cell Death". In development, apoptosis begins in the early blastocyst and is a developmental mechanism found throughout tissues in the embryo and fetus developmental stages. In addition to the many developmental roles this process is used in multicellular organisms to remove cells that are: aged, superfluous, infected, contain genetic errors or are transformed.
While the cellular morphological changes associated with this process are the same in all cells, there are many different signaling pathways that can "trigger" this process. They fall generally into two signalling classes either intrinsic or extrinsic to the cell. To describe "programmed cell death" as apoptosis was originally used in 1972 by Kerr, Wyllie and Currie.[2]
| Cell Biology Lecture - Cell Death
Some Recent Findings
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Developmental Examples
Blastocyst development
Removing cells from the developing inner cell mass.
|
Cell death in bovine blastocyst[4] |
Digit development
Removing cells between digits (fingers and toes) of the upper and lower limbs.
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Depletion of BMP signaling causes Interdigital syndactyly.[5] |
Bone development
During ossification removing chondrocytes.
- Links: Bone Development
Neural development
Removing excess or inappropriately connected neurons.
- Links: Neural
Ovary development
Removing excess primordial follicles from the ovary cortex.
- Links: Ovary Development
Mammary development
- Links: Mammary Gland
Nobel Prize 2002
The 2002 Nobel Prize in Physiology or Medicine went to three researchers who originally identified this mechanism in the genetic regulation of organ development and programmed cell death.
- Sydney Brenner (b 1927), Berkeley, CA, USA, established C. elegans as a novel experimental model organism. This provided a unique opportunity to link genetic analysis to cell division, differentiation and organ development – and to follow these processes under the microscope. Brenner's discoveries, carried out in Cambridge, UK, laid the foundation for this year's Prize.
- John Sulston (b 1942), Cambridge, England, mapped a cell lineage where every cell division and differentiation could be followed in the development of a tissue in C. elegans. He showed that specific cells undergo programmed cell death as an integral part of the normal differentiation process, and he identified the first mutation of a gene participating in the cell death process.
- Robert Horvitz (b 1947), Cambridge, MA, USA, has discovered and characterized key genes controlling cell death in C. elegans. He has shown how these genes interact with each other in the cell death process and that corresponding genes exist in humans.
- Links: Nobel Prize 2002
Apoptotic Cell Morphology
The following cellular changes occur in sequence during apoptosis.
- loss of cell membrane phospholipid asymmetry
- Condensation of chromatin
- Reduction in nuclear size JCB - Nucleus changes
- Internucleosomal DNA cleavage TUNEL staining
- DNA ladder
- shrinkage of the cell
- Cleavage of cytoskeletal proteins PNAS - Actin cleavage by ICE-like proteases
- note actin also binds DNase 1, cleavage may release this enzyme to further cleave DNA
- membrane blebbing
- breakdown of the cell into membrane-bound apoptotic bodies (apoptosomes)
- bodies then phagocytosed by other cells
Experimentally a number of different techniques have been developed and are now used to identify these changes.
- Links:
Apoptosis Regulators
Regulators can initiate or block apoptosis, the regulators shown block apoptosis.
Regulator → | Adaptor → | Effector | |||
---|---|---|---|---|---|
C. elegans | Ced-9 → | Ced-4 → | Ced-3 → | Death | |
Vertebrates | Bcl-2 → | Apaf-1 → | Caspase-9 → | Caspase-3 → | Death |
References
- ↑ <pubmed>17353361</pubmed>| PMC2064059 | J Cell Biol.
- ↑ <pubmed>4561027</pubmed>
- ↑ <pubmed>21966582</pubmed>
- ↑ <pubmed>21811561</pubmed>| PLoS One.
- ↑ <pubmed>17194222</pubmed>| PMC1713256
Textbooks
Molecular Biology of the Cell
Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter New York and London: Garland Science; c2002
- Molecular Biology of the Cell 4th ed. - IV. Internal Organization of the Cell Chapter 17. The Cell Cycle and Programmed Cell Death
- The Cell Cycle and Programmed Cell Death
- Programmed Cell Death (Apoptosis)
- Figure 17-37. Cell death
- Figure 17-47. Two ways in which survival factors suppress apoptosis
- Figure 17-42. Cell-cycle arrest or apoptosis induced by excessive stimulation of mitogenic pathways
- Figure 17-38. The caspase cascade involved in apoptosis
Molecular Cell Biology
Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E. New York: W. H. Freeman & Co.; c1999
- Molecular Cell Biology - Chapter 23. Cell Interactions in Development
- Cell Death and Its Regulation
- Figure 23-50. Current models of the intracellular pathways leading to cell death by apoptosis or to trophic factor–mediated cell survival in mammalian cells
- Movie: Apoptosis
The Cell- A Molecular Approach
Cooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000
- The Cell - A Molecular Approach - IV. Cell Regulation Chapter 13. Cell Signaling
- Regulation of Programmed Cell Death
Reviews
<pubmed></pubmed>
Articles
Search PubMed
Search Pubmed: developmental apoptosis | developmental cell death | apoptosis
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- UNSW Cell Biology - Lecture - Cell Death
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Cite this page: Hill, M.A. (2024, June 15) Embryology Developmental Mechanism - Apoptosis. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Developmental_Mechanism_-_Apoptosis
- © Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G