Toll (gene)
Encyclopedia
The Toll genes encode members of the Toll-like receptor
Toll-like receptor
Toll-like receptors are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors that recognize structurally conserved molecules derived from microbes...

 class of proteins. "Toll" is German
German language
German is a West Germanic language, related to and classified alongside English and Dutch. With an estimated 90 – 98 million native speakers, German is one of the world's major languages and is the most widely-spoken first language in the European Union....

 for "amazing" or "great". Mutants in the Toll gene were originally identified by 1995 Nobel Laureates 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...

 and Eric Wieschaus and colleagues in the fruit fly
Drosophilidae
Drosophilidae is a diverse, cosmopolitan family of flies, which includes fruit flies. Another family of flies called Tephritidae also includes fruit flies. The best known species of Drosophilidae is Drosophila melanogaster, within the genus Drosophila, and this species Is used extensively for...

 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...

in 1985, and cloned by the laboratory of Kathryn Anderson in 1988. Since then, eleven mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...

ian Toll genes have been identified.

In flies, Toll was first identified as a gene important in embryogenesis
Embryogenesis
Embryogenesis is the process by which the embryo is formed and develops, until it develops into a fetus.Embryogenesis starts with the fertilization of the ovum by sperm. The fertilized ovum is referred to as a zygote...

 in establishing the dorsal
Dorsum (biology)
In anatomy, the dorsum is the upper side of animals that typically run, fly, or swim in a horizontal position, and the back side of animals that walk upright. In vertebrates the dorsum contains the backbone. The term dorsal refers to anatomical structures that are either situated toward or grow...

-ventral axis. In 1996, Toll was found to have a role in the fly's immunity to fungal
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...

 infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

s. Both mammalian and invertebrate
Invertebrate
An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group...

 Toll genes are required for innate immunity
Innate immune system
The innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner...

.

Toll-like receptors in mammals were identified in 1997 at Yale University
Yale University
Yale University is a private, Ivy League university located in New Haven, Connecticut, United States. Founded in 1701 in the Colony of Connecticut, the university is the third-oldest institution of higher education in the United States...

 by Ruslan Medzhitov
Ruslan Medzhitov
Ruslan M. Medzhitov, Ph.D., the David W. Wallace Professor of Immunobiology at Yale School of Medicine, a member of Yale Cancer Center and a Howard Hughes Medical Institute investigator...

 and Charles Janeway
Charles Janeway
Charles Alderson Janeway, Jr. was a noted immunologist. A member of the National Academy of Sciences, he held a faculty position at Yale University's Medical School and was an HHMI Investigator....

. Concurrently, Bruce A. Beutler
Bruce A. Beutler
Bruce Alan Beutler is an American immunologist and geneticist. Together with Jules A. Hoffmann, they received one-half of the 2011 Nobel Prize in Physiology or Medicine, for "their discoveries concerning the activation of innate immunity" Bruce Alan Beutler (born December 29, 1957) is an American...

 and colleagues discovered that the Toll-like receptors (TLRs) act as the principal sensors of infection in mammals. This latter discovery hinged on the positional cloning of the mammalian lipopolysaccharide
Lipopolysaccharide
Lipopolysaccharides , also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.-Functions:LPS is the major...

(LPS) response locus, which identified the LPS receptor as Toll related protein TLR4.

The name of the gene family derives from Christiane Nüsslein-Volhard's 1985 exclamation, "" The exclamation, which translates as "That's amazing!" or "That's weird!", was in reference to the underdeveloped ventral portion of a fruit fly larva.
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