French flag model
Encyclopedia
Lewis Wolpert
Lewis Wolpert CBE FRS FRSL is a developmental biologist, author, and broadcaster.-Career:Wolpert was educated at the University of Witwatersrand , at Imperial College London, and at King's College London...
in the 1960s. A morphogen
Morphogen
A morphogen is a substance governing the pattern of tissue development, and the positions of the various specialized cell types within a tissue...
is rigorously defined as a signaling molecule that acts directly on cells (not through serial induction) to produce specific cellular responses dependent on morphogen concentration. During early development, morphogen gradients generate different cell types in distinct spatial order.
In the French flag model, the French flag
Flag of France
The national flag of France is a tricolour featuring three vertical bands coloured royal blue , white, and red...
is used to represent the effect of a morphogen on cell differentiation: a morphogen affects cell states based on concentration, these states are represented by the different colors of the French flag: high concentrations activate a "blue" gene, lower concentrations activate a "white" gene, with "red" serving as the default state in cells below the necessary concentration threshold.
The French Flag model was championed by the leading Drosophila biologist, Peter Lawrence
Peter Lawrence
Peter Anthony Lawrence FRS is a British developmental biologist at the Laboratory of Molecular Biology and the Zoology Department of the University of Cambridge...
. Christiane Nüsslein-Volhard
Christiane Nüsslein-Volhard
Christiane Nüsslein-Volhard is a German biologist who won the Albert Lasker Award for Basic Medical Research in 1991 and the Nobel Prize in Physiology or Medicine in 1995, together with Eric Wieschaus and Edward B...
identified the first morphogen, Bicoid
Drosophila embryogenesis
Drosophila embryogenesis, the process by which Drosophila embryos form, is a favorite model system for geneticists and developmental biologists studying embryogenesis. The small size, short generation time, and large brood size make it ideal for genetic studies. Transparent embryos facilitate...
, one of the transcription factors present in a gradient in the Drosophila syncitial embryo. Two labs, that of Gary Struhl and that of Stephen Cohen, then demonstrated that a secreted signaling protein, Decapentaplegic (the Drosophila homologue of Transforming Growth Factor Beta), acted as a morphogen during later stages of Drosophila development. substance governing the pattern of tissue development and, in particular, the positions of the various specialized cell types within a tissue. It spreads from a localized source and forms a concentration gradient across a developing tissue.
Well-known morphogens include: Decapentaplegic
Decapentaplegic
Decapentaplegic is a key morphogen involved in the development of the fruit fly Drosophila melanogaster. It is known to be necessary for the correct patterning of the fifteen imaginal discs, which are tissues that will become limbs and other organs and structures in the adult fly. It has also been...
/ Transforming growth factor beta, Hedgehog / Sonic Hedgehog
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
, Wingless
Wnt signaling pathway
The Wnt signaling pathway is a network of proteins best known for their roles in embryogenesis and cancer, but also involved in normal physiological processes in adult animals.-Discovery:...
/ Wnt
Wnt signaling pathway
The Wnt signaling pathway is a network of proteins best known for their roles in embryogenesis and cancer, but also involved in normal physiological processes in adult animals.-Discovery:...
, Epidermal growth factor
Epidermal growth factor
Epidermal growth factor or EGF is a growth factor that plays an important role in the regulation of cell growth, proliferation, and differentiation by binding to its receptor EGFR...
, and Fibroblast growth factor
Fibroblast growth factor
Fibroblast growth factors, or FGFs, are a family of growth factors involved in angiogenesis, wound healing, and embryonic development. The FGFs are heparin-binding proteins and interactions with cell-surface associated heparan sulfate proteoglycans have been shown to be essential for FGF signal...
.
Some of the earliest and best-studied morphogens are transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s that diffuse within early Drosophila melanogaster
Drosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...
(fruit fly) embryos. However, most morphogens are secreted proteins that signal between cells.
Morphogens are defined conceptually, not chemically, so simple chemicals such as retinoic acid
Retinol
Retinol is one of the animal forms of vitamin A. It is a diterpenoid and an alcohol. It is convertible to other forms of vitamin A, and the retinyl ester derivative of the alcohol serves as the storage form of the vitamin in animals....
may also act as morphogens.
External links
Excellent resources for further study of this topic include:- Interactive Fly
- Flybase
- Artificial Life model of multicellular morphogenesis with autonomously generated gradients for positional information
NCBI resources
From the National Center for Biotechnology InformationNational Center for Biotechnology Information
The National Center for Biotechnology Information is part of the United States National Library of Medicine , a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988 through legislation sponsored by Senator Claude Pepper...
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