Sonic hedgehog

3HO5, 3M1N, 3MXW646920423ENSG00000164690ENSMUSG00000002633Q15465Q62226NM_000193NM_001310462NM_009170NP_000184NP_001297391NP_033196Sonic hedgehog is a protein that in humans is encoded by the SHH ('sonic hedgehog') gene. Both the gene and the protein may also be found notated alternatively as 'Shh'.SHH and BMP gradients in the vertebrate neural tubeEctopic floor plate formationVentral neural domains in neural tube1vhh: A POTENTIAL CATALYTIC SITE WITHIN THE AMINO-TERMINAL SIGNALLING DOMAIN OF SONIC HEDGEHOG Sonic hedgehog is a protein that in humans is encoded by the SHH ('sonic hedgehog') gene. Both the gene and the protein may also be found notated alternatively as 'Shh'. Sonic hedgehog is one of three proteins in the mammalian signaling pathway family called hedgehog, 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 the development of some cancers. The hedgehog gene (hh) was first identified in the fruit-fly Drosophila melanogaster in the classic Heidelberg screens of Christiane Nüsslein-Volhard and Eric Wieschaus, as published in 1980. These screens, which led to them winning the Nobel Prize in 1995 along with developmental geneticist Edward B. Lewis, identified genes that control the segmentation pattern of the Drosophila embryos. The hh loss of function mutant phenotype causes the embryos to be covered with denticles, small pointy projections resembling the spines of a hedgehog. Investigations aimed at finding a hedgehog equivalent in vertebrates by Philip Ingham, Andrew P. McMahon, and Clifford Tabin, revealed three homologous genes. Two of these, desert hedgehog and Indian hedgehog, were named for species of hedgehogs, while sonic hedgehog was named after Sonic the Hedgehog, the protagonist of the eponymous video game franchise. The name was devised by Robert Riddle, who was a postdoctoral fellow at the Tabin Lab, after he saw a Sonic comic book his daughter owned. In the zebrafish, two of the three vertebrate hh genes are duplicated: SHH a, SHH b (formerly described as tiggywinkle hedgehog, named for Mrs. Tiggy-Winkle, a character from Beatrix Potter's books for children), ihha and ihhb (formerly described as echidna hedgehog, named for the spiny anteater and not for the echidna character Knuckles in the Sonic franchise). 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 and midline structures in the brain, spinal cord, the thalamus by the zona limitans intrathalamica the lungs, and the teeth. 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 at the zone of polarizing activity, which is located on the 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 tumors, including the embryonic cerebellar tumor, and medulloblastoma, as well as the progression of prostate cancer tumours. For SHH to be expressed in the developing embryo limbs, a morphogen called fibroblast growth factors must be secreted from the apical ectodermal ridge. 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 developing spinal cord. Specifically, SHH attracts retinal ganglion cell (RGC) axons at low concentrations and repels them at higher concentrations. The absence (non-expression) of SHH has been shown to control the growth of nascent hind limbs in cetaceans (whales and dolphins). The sonic hedgehog (SHH) signaling molecule assumes various roles in patterning the central nervous system (CNS) during vertebrate development. One of the most characterized functions of SHH is its role in the induction of the floor plate and diverse ventral cell types within the neural tube. The notochord, a structure derived from the axial mesoderm, produces SHH, which travels extracellularly to the ventral region of the neural tube and instructs those cells to form the floor plate. Another view for floor plate induction hypothesizes that some precursor cells located in the notochord are inserted into the neural plate before its formation, later giving rise to the floor plate. The neural tube itself is the initial groundwork of the vertebrate CNS, and the floor plate is a specialized structure and is located at the ventral midpoint of the neural tube. Evidence supporting the notochord as the signaling center comes from studies in which a second notochord is implanted near a neural tube in vivo, leading to the formation of an ectopic floor plate within the neural tube.