Sonic hedgehog homolog (SHH) is one of three proteins in the mammalian hedgehog family, the others being desert hedgehog (DHH) and Indian hedgehog (IHH). SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as in the growth of digits on limbs and organization of the brain. Sonic hedgehog is the best established example of a morphogen as defined by Lewis Wolpert's French flag model - a molecule that diffuses to form a concentration gradient and has different effects on the cells of the developing embryo depending on its concentration. SHH remains important in the adult. It controls cell division of adult stem cells and has been implicated in development of some cancers. Sonic the Hedgehog is a fictional hedgehog character that serves as the mascot of the Japanese video game company Sega. ... Image File history File links Shh_structure. ... Look up Hugo in Wiktionary, the free dictionary. ... This article is about the general scientific term. ... Short and long arms Chromosome. ... Chromosome 7 is one of the 23 pairs of chromosomes in humans. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... In chemistry, an amino acid is any molecule that contains both amino and carboxylic acid functional groups. ... The unified atomic mass unit (u), or dalton (Da), is a small unit of mass used to express atomic and molecular masses. ... Within a protein, a structural domain (domain) is an element of overall structure that is self-stabilizing and often folds independently of the rest of the protein chain. ... In an unbranched, chain-like biological molecule, such as a protein or a strand of RNA, a structural motif is a three-dimensional structural element or fold within the chain, which appears also in a variety of other molecules. ... A taxon (plural taxa), or taxonomic unit, is a grouping of organisms (named or unnamed). ... Homo sapiens (Latin: wise man) is the scientific name for the human species. ... Phyla Subkingdom Parazoa Porifera (sponges) Subkingdom Agnotozoa Placozoa Orthonectida Rhombozoa Subkingdom Metazoa Radiata Cnidaria Ctenophora - Comb jellies Bilateria Protostomia Acoelomorpha Platyhelminthes - Flatworms Nemertina - Ribbon worms Gastrotricha Gnathostomulida - Jawed worms Micrognathozoa Rotifera - Rotifers Acanthocephala Priapulida Kinorhyncha Loricifera Entoprocta Nematoda - Roundworms Nematomorpha - Horsehair worms Cycliophora Mollusca - Mollusks Sipuncula - Peanut worms Annelida - Segmented... A taxon (plural taxa) is an element of a taxonomy, e. ... There are about 210 distinct human cell types. ... Biological tissue is a collection of interconnected cells that perform a similar function within an organism. ... In cell biology, molecular biology and related fields, the word extracellular means outside the cell. It is used in contrast to intracellular (inside the cell). ... Drawing of a cell membrane A component of every biological cell, the cell membrane (or plasma membrane) is a thin and structured bilayer of phospholipid and protein molecules that envelopes the cell. ... Covalent redirects here. ... Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. ... The hedgehog signaling pathway is one of the key regulators of animal development conserved from flies to humans. ... This article is about the medical term. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... Cephalic disorders are congenital conditions that stem from damage to, or abnormal development of, the budding nervous system. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... National Center for Biotechnology Information logo The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Orders Subclass Monotremata Monotremata Subclass Marsupialia Didelphimorphia Paucituberculata Microbiotheria Dasyuromorphia Peramelemorphia Notoryctemorphia Diprotodontia Subclass Placentalia Xenarthra Dermoptera Desmostylia Scandentia Primates Rodentia Lagomorpha Insectivora Chiroptera Pholidota Carnivora Perissodactyla Artiodactyla Cetacea Afrosoricida Macroscelidea Tubulidentata Hyracoidea Proboscidea Sirenia The mammals are the class of vertebrate animals primarily characterized by the presence of mammary... The hedgehog signaling pathway is one of the key regulators of animal development conserved from flies to humans. ... In chemistry, a ligand is an atom, ion, or molecule (see also: functional group) that generally donates one or more of its electrons through a coordinate covalent bond to, or shares its electrons through a covalent bond with, one or more central atoms or ions (these ligands act as a... The hedgehog signaling pathway is one of the key regulators of animal development conserved from flies to humans. ... This article does not cite any references or sources. ... Organogenesis is a stage of animal development where the ectoderm, endoderm, and mesoderm are formed. ... Look up Limb in Wiktionary, the free dictionary. ... The human brain In animals, the brain (enkephalos) (Greek for in the skull), is the control center of the central nervous system, responsible for behavior. ... A morphogen is a substance governing the pattern of tissue development and, in particular, the positions of the various specialized cell types within a tissue. ... Lewis Wolpert Lewis Wolpert CBE FRS FRSL (born October 19, 1929) is a developmental biologist, author, and broadcaster. ... diffusion (disambiguation). ... For other uses, see Embryo (disambiguation). ... This does not adequately cite its references or sources. ... Stem cell division and differentiation. ... Cancers are caused by a series of mutations. ...

Some clinicians and scientists criticize giving genes frivolous or quirky names, calling it inappropriate that patients with "a serious illness or disability are told that they or their child have a mutation in a gene such as Sonic hedgehog." ^[1] Look up disability in Wiktionary, the free dictionary. ... For linguistic mutation, see Apophony. ...

Discovery

The hedgehog gene (hh) was first identified in the classic Heidelberg screens of Eric Wieschaus and Christiane Nusslein-Volhard, as published in 1978. These screens, which led to their winning the Nobel Prize in 1995 along with developmental geneticist Edward B. Lewis, identified genes that control the segmentation pattern of Drosophila melanogaster (fruit fly) embryos. The hh loss of function mutant phenotype causes the embryos to be covered with denticles (small pointy projections), much like a hedgehog. The hedgehog signaling pathway is one of the key regulators of animal development conserved from flies to humans. ... Eric F. Wieschaus (born June 8, 1947) is an American developmental biologist. ... Christiane Nüsslein-Volhard (born October 12, 1942 in Magdeburg) is a German biologist. ... A genetic screen (often shortened to screen) is a procedure or test to identify and select individuals who possess a phenotype of interest. ... Emil Adolf von Behring was the first person to receive the Nobel Prize in physiology or Medicine, for his work on the treatment of diphtheria. ... Edward B. Lewis (May 20, 1918 – July 21, 2004) was an American geneticist, the winner of the 1995 Nobel Prize in Medicine. ... Binomial name Meigen, 1830[1] Drosophila melanogaster (from the Greek for black-bellied dew-lover) is a two-winged insect that belongs to the Diptera, the order of the flies. ... For other uses, see Embryo (disambiguation). ... This article is about biological mutants. ... Individuals in the mollusk species Donax variabilis show diverse coloration and patterning in their phenotypes. ... Genera Atelerix Erinaceus Hemiechinus Mesechinus Paraechinus A hedgehog is any of the small spiny mammals of the subfamily Erinaceinae and the order Erinaceomorpha. ...

Investigations aimed at finding a hedgehog equivalent in mammals revealed three homologous genes. The first two discovered, desert hedgehog and Indian hedgehog, were named for species of hedgehogs, while sonic hedgehog was named after Sega's video game character Sonic the Hedgehog. In zebrafish, the orthologues of the three mammalian hh genes are: shh a, shh b (formerly described as tiggywinkle hedgehog named for a character from Beatrix Potter's books for children.), and indian hedgehog b (formerly described as echidna hedgehog, named for the spiny anteater. In biology, homology is any similarity between structures that is due to their shared ancestry. ... Genera Atelerix Erinaceus Hemiechinus Mesechinus Paraechinus A hedgehog is any of the small spiny mammals of the subfamily Erinaceinae and the order Erinaceomorpha. ... This article is about the video game company. ... Sonic the Hedgehog ), trademarked Sonic The Hedgehog,[4] is a video game character and the hero of a video game series released by Sega, as well as numerous spin-off comics, cartoons and books. ... Binomial name Danio rerio (Hamilton-Buchanan, 1822) The Zebra Danio or Zebrafish (Brachydanio rerio or Danio rerio) is a tropical fish, commonly kept in aquaria and used for scientific research, belonging to the minnow family (Cyprinidae). ... Orthologues is the plural of ortholog, which is a gene in Homology (biology). ... Helen Beatrix Potter (28 July 1866 – 22 December 1943) was an English author and illustrator, botanist, and conservationist, best known for her childrens books, which featured animal characters such as Peter Rabbit. ... For other senses of this word, see echidna (disambiguation). ...

Function

Of the hh homologues, shh has been found to have the most critical roles in development, acting as a morphogen involved in patterning many systems, including the limb^[2] and midline structures in the brain^[3] and spinal cord^[4] and the thalamus by the zona limitans intrathalamica^[5]. Mutations in the human sonic hedgehog gene, SHH, cause holoprosencephaly type 3 (HPE3) as a result of the loss of the ventral midline. Sonic hedgehog is secreted by the zone of polarizing activity (ZPA), which is located on posterior side of a limb bud in an embryo. The sonic hedgehog transcription pathway has also been linked to the formation of specific kinds of cancerous tumours. A morphogen is a substance governing the pattern of tissue development and, in particular, the positions of the various specialized cell types within a tissue. ... The human brain In animals, the brain (enkephalos) (Greek for in the skull), is the control center of the central nervous system, responsible for behavior. ... The Spinal cord nested in the vertebral column. ... The thalamus (from Greek θάλαμος = bedroom, chamber, IPA= /ˈθæləməs/) is a pair and symmetric part of the brain. ... The zona limitans intrathalamica (ZLI) is a transverse boundary located between the prethalamus (previously also known as ventral thalamus) and the functional distinct thalamus (dorsal thalamus ). Besides its morphological characteristics, it bears the hallmarks of a signalling centre. ... For other uses, see Gene (disambiguation). ... Cephalic disorders are congenital conditions that stem from damage to, or abnormal development of, the budding nervous system. ...

More recently, sonic hedgehog has also been shown to act as an axonal guidance cue. It has been demonstrated that Shh attracts commissural axons at the ventral midline of the developping spinal cord.^[6] Specifically, Shh attracts retinal ganglion cell (RGC) axons at low concentrations and repels them at higher concentrations.^[7] The absence (non-expression) of Shh has been shown to control the growth of nascent hind limbs in cetaceans^[8] (whales and dolphins). This article or section does not cite any references or sources. ... A ganglion cell (or sometimes called a gangliocyte) is a type of neuron located in the retina that receives visual information from photoreceptors via various intermediate cells such as bipolar cells, amacrine cells, and horizontal cells. ... Suborders Mysticeti Odontoceti (see text) The order Cetacea includes whales, dolphins and porpoises. ... This article is about the animal. ... For other uses, see Dolphin (disambiguation). ...

Processing

Processing of SHH.

SHH undergoes a series of processing steps before it is secreted from the cell. Newly synthesised SHH weighs 45 kDa and is referred to as the preproprotein. As a secreted protein it contains a short signal sequence at its N-terminus, which is recognised by the signal recognition particle during the translocation into the endoplasmic reticulum (ER), the first step in protein secretion. Once translocation is complete, the signal sequence is removed by signal peptidase in the ER. There SHH undergoes autoprocessing to generate a 20 kDa N-terminal signaling domain (SHH-N) and a 25 kDa C-terminal domain with no known signaling role.^[9] The cleavage is catalysed by a protease within the C-terminal domain. During the reaction, a cholesterol molecule is added to the C-terminus of SHH-N.^[10] Thus the C-terminal domain acts as an intein and a cholesterol transferase. Another hydrophobic moiety, a palmitate, is added to the alpha-amine of N-terminal cysteine of SHH-N. This modification is required for efficient signaling, resulting in 30-fold increase in potency over the non-palmitylated form.^[11] Image File history File links Shh_processing. ... Image File history File links Shh_processing. ... The unified atomic mass unit (u), or dalton (Da), is a small unit of mass used to express atomic and molecular masses. ... A signal peptide is a short (15-60 amino acids long) peptide chain that directs the post transrational transport of a protein. ... The signal recognition particle (SRP) is a protein-RNA complex that recognizes and transports specific proteins to the endoplasmic reticulum in eukaryotes and the plasma membrane in prokaryotes. ... The endoplasmic reticulum or ER is an organelle found in all eukaryotic cells that is an interconnected network of tubules, vesicles and cisternae that is responsible for several specialized functions: Protein translation, folding, and transport of proteins to be used in the cell membrane (e. ... Secretion is the process of segregating, elaborating, and releasing chemicals from a cell, or a secreted chemical substance or amount of substance. ... Proteases (proteinases, peptidases, or proteolytic enzymes) are enzymes that break peptide bonds between amino acids of proteins. ... Cholesterol is a sterol (a combination steroid and alcohol). ... An intein is a segment of a protein that is able to excise itself and rejoin the remaining portions (the exteins) with a peptide bond. ... In chemistry, hydrophobic or lipophilic species, or hydrophobes, tend to be electrically neutral and nonpolar, and thus prefer other neutral and nonpolar solvents or molecular environments. ... Look up moiety in Wiktionary, the free dictionary. ... Palmitic acid, or hexadecanoic acid in IUPAC nomenclature, is one of the most common saturated fatty acids found in animals and plants. ... Cysteine is a naturally occurring, sulfur-containing amino acid that is found in most proteins, although only in small quantities. ...

See also

• Zbtb7, a gene which was originally named Pokemon after the video game Pokémon

Zbtb7, originally named Pokemon, is a gene that may act as a master switch for cancer. ... The official Pokémon logo. ...

Further reading

• Dorus S, Anderson JR, Vallender EJ, et al (2006). "Sonic Hedgehog, a key development gene, experienced intensified molecular evolution in primates". Hum. Mol. Genet. 15 (13): 2031-7. doi:10.1093/hmg/ddl123. PMID 16687440. 
• Gilbert, Scott F. (2000). Developmental biology, 6th edition, Sunderland, Mass: Sinauer Associates. ISBN 0-87893-243-7. 

A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ...

External links

• An introductory article on shh at Davidson College

Davidson College is a private liberal arts college for 1,700 students in Davidson, North Carolina, USA. Both the town and college were named for Brigadier General William Lee Davidson, a Revolutionary War commander. ...

References