Developmental Mechanism - Apoptosis
|Embryology - 19 Feb 2020 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Developmental Examples
- 4 Worm Development
- 5 Renal Development
- 6 Nobel Prize 2002
- 7 Adult Examples
- 8 Apoptotic Cell Morphology
- 9 Apoptosis Regulators
- 10 Necrosis
- 11 References
- 12 External Links
- 13 Glossary Links
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.PubmedParser error: The PubmedParser extension received invalid XML data. ()
Some Recent Findings
|More recent papers|
This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.
Search term: Development Apoptosis
|These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.|
|Removing cells from the developing inner cell mass.
Cell death in bovine blastocyst
Cloacal Membrane Development
The initial cloaca is the common early endoderm lined space of the hindgut that will later become partitioned by a septum into a dorsal gastrointestinal component (rectum) and ventral renal/genital component (urogenital sinus). Located at the inferior end of the cloaca is the cloacal membrane, that also forms part of the embryo surface. The cloacal membrane is formed during gastrulation by ectoderm and endoderm without a middle (intervening) layer of mesoderm, and later degenerates by apoptosis after cloacal septation in mammals.
- Links: cloacal membrane
|Removing cells between digits (fingers and toes) of the upper and lower limbs.
Interdigital apoptosis in the mous hindlimb.
During ossification removing chondrocytes.
- Links: bone
Removing excess or inappropriately connected neurons.
- Links: neural
Removing excess primordial follicles from the ovary cortex.
- Links: ovary
Full involution returns the gland to a pre-pregnant state. ECM, extracellular matrix.
- Links: mammary gland
The overview diagram above shows the fate of each individual cell in the developing c. elegans.
- the "X" indicates cells that die by apoptosis during development.
- Zygote (P0 cell) divides into two daughter cells (AB and P1 cells).
- These two daughter cells then divide into the next generation.
Note the above image is not at a readable resolution, to view see large readable version (10,389 × 1,336 pixels). Embryonic cell lineage developed by J .E. Sulston, E. Schierenberg, J. G. White, J. N. Thomson.
- Links: Renal
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
|This movie from an in vitro experimental bacterial infection of Hela cells with Neisseria gonorrhoeae shows the cells dying by apoptosis.
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.
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|
p63 (tumor protein p63) gene (3q28) encodes a transcription factor with multiple isotypes that transactivate p53 reporter genes and induce apoptosis. For example, during palate development p63 can exert spatio-temporal control of palatal epithelial cell fate to prevent cleft palate 
- Links: OMIM p63
Necrosis (Greek, nekros = corpse) is not a form of developmental cell death, but a pathological cell death from extrinsic injury (tissue damage) and is irreversible. Necrosis is induced by tumor necrosis factor, double-stranded RNA, viral infection or bacterial infection toxins.
In the early stages, cell and organelles (mitochondria) swell (oncosis) (Greek, onkos = 'swelling') previously described as a separate form of cell death. This is due to disruption of plasma membrane leading to cell contents leak out leading to inflammation and necrosis.
In the late stages, there is a loss of cell membrane integrity, finally cell disintegration. This cell lysis can also trigger an inflammatory response, leading to further inflammation and damage, and triggering a cycle of death
- Bacteria - S. aureus - pore-forming secreted toxins can induce necrosis
- Prothymosin-alpha 1 - (ProT) inhibits necrosis, switches cells from necrosis to apoptosis
- Ueda H, Fujita R, Yoshida A, Matsunaga H & Ueda M. (2007). Identification of prothymosin-alpha1, the necrosis-apoptosis switch molecule in cortical neuronal cultures. J. Cell Biol. , 176, 853-62. PMID: 17353361 DOI.
- Shinotsuka N, Yamaguchi Y, Nakazato K, Matsumoto Y, Mochizuki A & Miura M. (2018). Caspases and matrix metalloproteases facilitate collective behavior of non-neural ectoderm after hindbrain neuropore closure. BMC Dev. Biol. , 18, 17. PMID: 30064364 DOI.
- Koto A & Miura M. (2011). Who lives and who dies: Role of apoptosis in quashing developmental errors. Commun Integr Biol , 4, 495-7. PMID: 21966582 DOI.
- Leidenfrost S, Boelhauve M, Reichenbach M, Güngör T, Reichenbach HD, Sinowatz F, Wolf E & Habermann FA. (2011). Cell arrest and cell death in mammalian preimplantation development: lessons from the bovine model. PLoS ONE , 6, e22121. PMID: 21811561 DOI.
- Miller SA, Clark C, Cooney R, Crary E & Payzant W. (1998). Apoptosis fenestrates chick cloacal membrane and occluded rectal cord and may have a minor role in removal of pharyngeal membranes. Ann. N. Y. Acad. Sci. , 857, 268-71. PMID: 9917854
- Sasaki C, Yamaguchi K & Akita K. (2004). Spatiotemporal distribution of apoptosis during normal cloacal development in mice. Anat Rec A Discov Mol Cell Evol Biol , 279, 761-7. PMID: 15278947 DOI.
- Bandyopadhyay A, Tsuji K, Cox K, Harfe BD, Rosen V & Tabin CJ. (2006). Genetic analysis of the roles of BMP2, BMP4, and BMP7 in limb patterning and skeletogenesis. PLoS Genet. , 2, e216. PMID: 17194222 DOI.
- Watson CJ. (2006). Involution: apoptosis and tissue remodelling that convert the mammary gland from milk factory to a quiescent organ. Breast Cancer Res. , 8, 203. PMID: 16677411 DOI.
- Richardson R, Mitchell K, Hammond NL, Mollo MR, Kouwenhoven EN, Wyatt ND, Donaldson IJ, Zeef L, Burgis T, Blance R, van Heeringen SJ, Stunnenberg HG, Zhou H, Missero C, Romano RA, Sinha S, Dixon MJ & Dixon J. (2017). p63 exerts spatio-temporal control of palatal epithelial cell fate to prevent cleft palate. PLoS Genet. , 13, e1006828. PMID: 28604778 DOI.
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
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- UNSW Cell Biology - Lecture - Cell Death
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Cite this page: Hill, M.A. (2020, February 19) Embryology Developmental Mechanism - Apoptosis. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Developmental_Mechanism_-_Apoptosis
- © Dr Mark Hill 2020, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G