関: Shh

WordNet

a male human offspring; "their son became a famous judge"; "his boy is taller than he is" (同)boy
relating to audible sound; "a sonic wave"
(of speed) having or caused by speed approximately equal to that of sound in air at sea level; "a sonic boom" (同)transonic
small nocturnal Old World mammal covered with both hair and protective spines (同)Erinaceus europaeus, Erinaceus europeaeus

PrepTutorEJDIC

『息子』・《複数形で》(男子の)子孫・《文》《比喩(ひゆ)的に》(場所・主義などの)子,後継者・《年長者が年少者に呼び掛けて》・お前さん・《the S-》イエスキリスト
音の(に関する) / 音速の
ハリネズミ

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/11/13 18:05:21」(JST)

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この項目では、遺伝子について記述しています。セガのゲームキャラクターについては「ソニック・ザ・ヘッジホッグ」をご覧ください。

ソニック・ヘッジホッグのシグナルドメイン（N末側）の立体構造

ソニック・ヘッジホッグ (Sonic hedgehog, SHH) は、ヘッジホッグ (HH) ファミリーに属する5種類のタンパク質の内の1つ。これをコーディングする遺伝子＝ソニック・ヘッジホッグ遺伝子は、shhと小文字で表記する。このファミリーの他のタンパク質には、哺乳類ではデザート・ヘッジホッグ (Desert Hedgehog, DHH)、インディアン・ヘッジホッグ (Indian Hedgehog, IHH)があり、魚類ではエキドナ・ヘッジホッグ (Echidna Hedgehog, EHH) とティギーウィンクル・ヘッジホッグ (Tiggywinkle Hedgehog, TwHH) がある。

ヘッジホッグ遺伝子 (hh) は最初にエリック・ヴィーシャウスとクリスティアーネ・ニュスライン＝フォルハルトの古典的なハイデルベルク・スクリーンにより同定されて、1978年に発表された。 2人が1995年のノーベル生理学・医学賞を得たこれらのスクリーニングで、ショウジョウバエ (Drosophila melanogaster) の胚の分節パターンをコントロールするこの遺伝子が同定された。hh遺伝子の機能を失った変異体の表現型の胚は小さな歯の様な突起物（歯状突起）が密集しており、ヘッジホッグ（ハリネズミ）という名前が付いた。

名称

哺乳類には3種類の相同遺伝子があり、先に見つかった2種類、デザート及びインディアン・ヘッジホッグは実在するハリネズミの種類から命名された一方、ソニック・ヘッジホッグはセガ・ジェネシス（日本でのメガドライブ）のキャラクターのソニック・ザ・ヘッジホッグから名づけられた。後にゼブラフィッシュから見つかった2種類についての命名は、エキドナ・ヘッジホッグがハリモグラ^[1]から、ティギーウィンクル・ヘッジホッグがビアトリクス・ポター作の絵本のキャラクター名、ティギーおばさん (Mrs. Tiggy-Winkle) から来ている。

機能

これらの遺伝子から合成されるHHタンパク質相同体の中で、SHHは発生において最も重要なモルフォゲンとして、四肢や、脳脊髄正中線構造などの、多くの器官系のデザインを形成する役割がある。

ヒト・ソニック・ヘッジホッグ遺伝子の変異では、腹側正中線の欠失が生じて全前脳胞症 (HPE) を引きおこすほか、シス調節エレメントの変化が原因で多指症になることなどが知られている

参照

ポケモン遺伝子 - ゲームに名前が因む他の遺伝子、Zbtb7の旧称。
ピカチュリン - 視覚情報伝達に必須のタンパク質で、動体視力の優劣を司る。ポケモンに登場するキャラクターのピカチュウに因んで付けられた。

注釈

^ なお、上述のゲーム作品「ソニックシリーズ」には、ナックルズ・ザ・エキドゥナというハリモグラのキャラクターも登場する。

外部リンク

An introductory article on shh

この「ソニック・ヘッジホッグ」は、生物学に関連した書きかけ項目です。この記事を加筆・訂正などしてくださる協力者を求めています（プロジェクト:生命科学／Portal:生物学）。

wiki en

[Wiki en表示]

For the video game character, see Sonic the Hedgehog (character).

Sonic hedgehog homolog (SHH) 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 development of some cancers.

Discovery

The hedgehog gene (hh) was first identified in the classic Heidelberg screens of Christiane Nusslein-Volhard, as published in 1980. These screens, which led to her 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), resembling a hedgehog.

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.^[1] In zebrafish, the orthologues of the three mammalian hh genes are: shh a,^[2] shh b,^[3] (formerly described as tiggywinkle hedgehog named for Mrs. Tiggy-Winkle, a character from Beatrix Potter's books for children), and indian hedgehog b^[4] (formerly described as echidna hedgehog, named for the spiny anteater, though this may have also been a playful reference to Knuckles the Echidna, another character from the Sonic the Hedgehog series of video games).

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^[5] and midline structures in the brain,^[6] spinal cord,^[7] the thalamus by the zona limitans intrathalamica^[8] and the teeth.^[9] 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 (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.

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 developing spinal cord.^[10] Specifically, Shh attracts retinal ganglion cell (RGC) axons at low concentrations and repels them at higher concentrations.^[11] The absence (non-expression) of Shh has been shown to control the growth of nascent hind limbs in cetaceans^[12] (whales and dolphins).

Patterning of the central nervous system

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.^[13] 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.^[14] Another view for floor plate induction hypothesize that some precursor cells located in notochord are inserted into the neural plate before its formation, later giving rise to floor plate.^[15]

The neural tube itself is the initial groundwork of the vertebrate CNS, and the floor plate is a specialized structure 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.^[16]

Shh and BMP gradients in the vertebrate neural tube

Ectopic floor plate formation

Ventral neural domains in neural tube

Sonic hedgehog is the secreted protein which mediates signaling activities of notochord and floor plate.^[17] Studies involving ectopic expression of Shh in vitro ^[18] and in vivo ^[19] results in floor plate induction, and differentiation of motor neuron and ventral interneurons. On the other hand, mice mutant for Shh lack ventral spinal cord characteristics.^[20]In vitro blocking of Shh signaling using antibody against it shows similar phenotypes.^[19] Shh exerts its effects in a concentration-dependent manner,^[21] so that a high concentration of Shh results in a local inhibition of cellular proliferation.^[22] This inhibition causes the floor plate to become thin compared to the lateral regions of the neural tube. Lower concentration of Shh results in cellular proliferation and induction of various ventral neural cell types.^[19] Once the floor plate is established, cells residing in this region will subsequently express Shh themselves ^[22] generating a concentration gradient within the neural tube. Although there is no direct evidence of a Shh gradient, there is indirect evidence via the visualization of Patched (Ptc) gene expression, which encodes for the ligand binding domain of Shh receptor,^[23] throughout the ventral neural tube.^[24] In vitro studies show that incremental two-threefold changes in Shh concentration give rise to motor neuron and different interneuronal subtypes as found in the ventral spinal cord.^[25] These incremental changes in vitro correspond to the distance of domains from the signaling tissue (notochord and floor plate) which subsequently differentiates into different neuronal subtypes as it occurs in vitro.^[26]

Shh gradient and Gli activity in the vertebrate neural tube.

Graded Shh signaling is suggested to be mediated through Gli family of proteins which are vertebrate homologues of Drosophila zinc-finger-containing transcription factor Cubitus interruptus (Ci) . Ci is crucial mediator of headgehog (Hh) signaling in Drosophila.^[27] In vertebrates three different Gli proteins are present,viz. Gli1, Gli2 and Gli3, which are expressed in the neural tube.^[28] Mice mutant for Gli1 show normal spinal cord development suggesting that it is dispensable for mediating Shh acitivity.^[29] Gli2 mutant mice show abnormalities in the ventral spinal cord with severe defects in floor plate and ventral most interneurons (V3).^[30] Gli3 antagonizes Shh function in dose dependent manner promoting dorsal neuronal subtypes. Shh mutant phenotype can be rescued in Shh/Gli3 double mutant.^[31] Gli proteins have a C-terimnal activation domain and an N-terminal repressive domain.^[28]^[32] Shh is suggested to promote activation function of Gli2 and inhibit repressive activity of Gli3. Shh also seems to activate the activation function of Gli3 but this acitivity is not strong enough.^[31] The graded concentration of Shh gives rise to graded acitivity of Gli 2 and Gli3, which promote ventral and dorsal neuronal subtypes in the ventral spinal cord. Evidence from Gli3 and Shh/Gli3 mutants show that Shh primarily regulates the spatial restriction of progenitor domains rather than being inductive as Shh/Gli3 mutant shows intermixing of cell types.^[31]^[33]

Shh also induces other proteins with which it interacts and these interactions can influence the sensitivity of cell towards Shh. Hedgehog-interacting protein (Hhip) is induced by Shh which in turn attenuates it's signaling activity.^[34] Vitronectin is another protein that is induced by Shh and it acts as an obligate co-factor for Shh signaling in the neural tube.^[35]

There are five distinct progenitor domains in the ventral neural tube, viz. V3 interneuron, motor neurons(MN), V2, V1, V0 interneurons (in ventral to dorsal order).^[25] These different progenitor domains are established by "communication" between different classes of homeobox transcription factors. These transcription factors respond to Shh gradient concentration. Depending upon the nature of their interaction with Shh, they are classified into two groups, class I and class II, and are composed of members from the Pax, Nkx, Dbx, and Irx families.^[22] Class I proteins are repressed at different threshold of Shh, delineating ventral boundaries of progenitor domains; while class II proteins are activated at different thresholds of Shh, delineating the dorsal limit of domains. Selective cross-repressive interactions between class I and class II proteins give rise to five cardinal ventral neuronal subtypes.^[36]

It is important to note that Shh is not the only signaling molecule exerting an effect on the developing neural tube. Many other molecules, pathways, and mechanisms are active (e.g. RA, FGF, BMP), and complex interactions between Shh and other molecules are possible.BMPs are suggested to play a critical role in determining the sensitivity of neural cell to Shh signaling. Evidence supporting this comes from studies done using BMP inhibitors which ventralize the fate of the neural plate cell for a given Shh concentration.^[37] On the other hand, mutation in BMP antagonist (such as noggin )produces severe defects in ventral most characteristics of the spinal cord followed by ectopic expression of BMP in the ventral neural tube.^[38] Interaction of Shh with Fgf and RA have yet not been studied in molecular detail.

Morphogenetic activity

The concentration and time dependent cell fate determining activity of Shh in the ventral neural tube makes it a prime example of a morphogen. In vertebrates, Shh signaling in the ventral portion of the neural tube is most notably responsible for the induction of floor plate cells and motor neurons.^[39]

Shh emanates from the notochord and ventral floor plate of the developing neural tube to create a concentration gradient that spans the dorso-ventral axis.^[40] Higher concentrations of the Shh ligand are found in the most ventral aspects of the neural tube and notochord, while lower concentrations are found in the more dorsal regions of the neural tube.^[40] The Shh concentration gradient has been visualized in the neural tube of mice engineered to express a Shh::GFP fusion protein to show this graded distribution of Shh during the time of ventral neural tube patterning.^[41]

It is thought that the Shh gradient works to elicit multiple different cell fates by a concentration and time dependent mechanism that induces a variety of transcription factors in the ventral progenitor cells.^[40]^[41] Each of the ventral progenitor domains expresses a highly individualized combination of transcription factors: Nkx2.2, Olig2, Nkx6.1, Nkx 6.2, Dbx1, Dbx2, Irx3, Pax6, and Pax7, that is regulated by the Shh gradient. These transcription factors are induced sequentially along the Shh concentration gradient with respect to the amount and time of exposure to Shh ligand.^[40] As each population of progenitor cells responds to the different levels of Shh protein, they begin to express a unique combination of transcription factors that leads to neuronal cell fate differentiation. This Shh induced differential gene expression creates sharp boundaries between the discrete domains of transcription factor expression which ultimately patterns the ventral neural tube.^[40]

The spatial and temporal aspect of the progressive induction of genes and cell fates in the ventral neural tube is illustrated by the expression domains of two of the most well characterized transcription factors Olig2, and Nkx2.2.^[40] Early in development the cells at the ventral midline have only been exposed to a low concentration of Shh for a relatively short time and express the transcription factor Olig2.^[40] The expression of Olig2 rapidly expands in a dorsal direction concomitantly with the continuous dorsal extension of the Shh gradient over time.^[40] However, as the morphogenetic front of Shh ligand moves and begins to grow more concentrated, cells that are exposed to higher levels of the ligand respond by switching off Olig2 and turning on Nkx2.2.^[40] Thus, Creating a sharp boundary between the cells expressing the transcription factor Nkx2.2 ventral to the cells expressing Olig2. It is in this way that each of domains of the six progenitor cell populations are thought to be successively patterned throughout the neural tube by the Shh concentration gradient.^[40]

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.^[42] 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.^[43] 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.^[44]

Robotnikinin

A potential inhibitor of the Hedgehog signaling pathway has been found and dubbed 'Robotnikinin', in honor of Sonic the Hedgehog's nemesis, Dr. Ivo "Eggman" Robotnik.

Criticism of the name

Some clinicians and scientists criticize giving genes frivolous, whimsical, 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."^[45]^[46]

References

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^ McMahon JA, Takada S, Zimmerman LB, Fan CM, Harland RM, McMahon AP. (May 1998). "Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite.". Genes Dev 12 (10): 1438–52. doi:10.1101/gad.12.10.1438. PMC 316831. PMID 9585504. //www.ncbi.nlm.nih.gov/pmc/articles/PMC316831/.
^ Roelink H, Porter JA, Chiang C, Tanabe Y, Chang DT, Beachy PA, Jessel TM (May 1995). "Floor Plate and Motor Neuron Induction by Different Concentrations of the Amino-Terminal Cleavage Product of Sonic Hedgehog Autoproteolysis". Cell 81 (3): 445–455. doi:10.1016/0092-8674(95)90397-6. PMID 7736596.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j Ribes V, Briscoe J (August 2009). "Establishing and interpreting Graded Sonic Hedgehog during Vertebrate Neural Tube Patterning: The Role of Negative Feedback". Cold Spring Harb Perspect Biol 1(2): a002014 (2): a002014. doi:10.1101/cshperspect.a002014. PMC 2742090. PMID 20066087. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2742090/.
^ ^a ^b Chamberlain CE, Jeong J, Guo C, Allen BL, McMahon AP (March 2008). "Notochord-derived Shh concentrates in close association with the apically positioned basal body in neural target cells and forms a dynamic gradient during neural patterning". Development 135 (6): 1097–1106. doi:10.1242/dev.013086. PMID 18272593.
^ Bumcrot DA, Takada R and McMahon AP (1 April 1995). "Proteolytic processing yields two secreted forms of sonic hedgehog". Mol Cell Biol. 15 (4): 2294–2303. PMC 230457. PMID 7891723. //www.ncbi.nlm.nih.gov/pmc/articles/PMC230457/.
^ Porter JA, Young KE and Beachy PA (1996). "Cholesterol modification of hedgehog signaling proteins in animal development". Science 274 (5285): 255–259. doi:10.1126/science.274.5285.255. PMID 8824192.
^ Pepinsky RB, Zeng C, Wen D, Rayhorn P, Baker DP, Williams KP, Bixler SA, Ambrose CM, Garber EA, Miatkowski K et al. (1998). "Identification of a palmitic acid-modified form of human Sonic hedgehog". J Biol Chem 273 (22): 14037–14045. doi:10.1074/jbc.273.22.14037. PMID 9593755. http://www.jbc.org/cgi/content/full/273/22/14037.
^ Maclean K (January 2006). "Humour of gene names lost in translation to patients". Nature 439 (7074): 266. doi:10.1038/439266d. PMID 16421543.
^ Cohen MM (July 2006). "Problems in the naming of genes". Am. J. Med. Genet. A 140 (13): 1483–4. doi:10.1002/ajmg.a.31264. PMID 16718675.

External links

An introductory article on shh at Davidson College
SHH at The GDB Human Genome Database
Rediscovering biology: Unit 7, Genetics of development. Expert interview transcripts, interview with John Incardona, PhD. explanation of the discovery and naming of the sonic hedgehog gene
‘Sonic Hedgehog’ sounded funny, at first. New York Times, November 12, 2006.
GeneReviews/NCBI/NIH/UW entry on Anophthalmia / Microphthalmia Overview

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 顔面裂および全前脳胞症 facial clefts and holoprosencephaly
2. 口唇口蓋裂の病因、出生前診断、産科管理、および再発 etiology prenatal diagnosis obstetrical management and recurrence of orofacial clefts
3. 進行した皮膚扁平上皮癌および基底細胞癌の全身療法 systemic treatment of advanced cutaneous squamous and basal cell carcinomas
4. 腫瘍学の最新情報 whats new in oncology
5. 母斑性基底細胞癌症候群 nevoid basal cell carcinoma syndrome

English Journal

Inhibition of the sonic hedgehog pathway by cyplopamine reduces the CD133+/CD15+ cell compartment and the in vitro tumorigenic capability of neuroblastoma cells.

Schiapparelli P, Shahi MH, Enguita-German M, Johnsen JI, Kogner P, Lazcoz P, Castresana JS.SourceBrain Tumor Biology Unit-CIFA, University of Navarra School of Sciences, Pamplona, Spain.
Cancer letters.Cancer Lett.2011 Nov 28;310(2):222-31. Epub 2011 Jul 18.
Sonic hedgehog (Hh) developmental pathway deregulation has been proven to play an essential role in several malignancies as neuroblastoma. We found that Hh signaling is active in neuroblastoma, as most pathway components, including GLI1, were expressed in cell lines and tumor samples. Furthermore, S
PMID 21803487

Noggin null allele mice exhibit a microform of holoprosencephaly.

Lana-Elola E, Tylzanowski P, Takatalo M, Alakurtti K, Veistinen L, Mitsiadis TA, Graf D, Rice R, Luyten FP, Rice DP.AbstractHoloprosencephaly (HPE) is a heterogeneous craniofacial and neural developmental anomaly characterized in its most severe form by the failure of the forebrain to divide. In humans, HPE is associated with disruption of Sonic hedgehog and Nodal signaling pathways, but the role of other signaling pathways has not yet been determined. In this study, we analyzed mice which, due to the lack of the Bmp antagonist Noggin, exhibit elevated Bmp signaling. Noggin(-/-) mice exhibited a solitary median maxillary incisor that developed from a single dental placode, early midfacial narrowing as well as abnormalities in the developing hyoid bone, pituitary gland and vomeronasal organ. In Noggin(-/-) mice, the expression domains of Shh, as well as the Shh target genes Ptch1 and Gli1, were reduced in the frontonasal region at key stages of early facial development. Using E10.5 facial cultures, we show that excessive BMP4 results in reduced Fgf8 and Ptch1 expression. These data suggest that increased Bmp signaling in Noggin(-/-) mice results in downregulation of the hedgehog pathway at a critical stage when the midline craniofacial structures are developing, which leads to a phenotype consistent with a microform of HPE.
Human molecular genetics.Hum Mol Genet.2011 Oct 15;20(20):4005-15. Epub 2011 Aug 5.
Holoprosencephaly (HPE) is a heterogeneous craniofacial and neural developmental anomaly characterized in its most severe form by the failure of the forebrain to divide. In humans, HPE is associated with disruption of Sonic hedgehog and Nodal signaling pathways, but the role of other signaling pathw
PMID 21821669

Japanese Journal

Hedgehog阻害剤,SMO阻害剤 (特集新しい作用機序の分子標的薬剤)

橋本淳
腫瘍内科 7(5), 438-442, 2011-05
NAID 40018890370

Sonic hedgehog signaling regulates actin cytoskeleton via Tiam1-Rac1 cascade during spine formation.

Sasaki Nobunari,Kurisu Junko,Kengaku Mineko
Molecular and cellular neurosciences 45(4), 335-344, 2010-12
… The sonic hedgehog (Shh) pathway has essential roles in several processes during development of the vertebrate central nervous system (CNS). …
NAID 120002647342

Related Pictures

★リンクテーブル★

リンク元	「ソニックヘッジホッグ」
関連記事	「hedgehog」

「ソニックヘッジホッグ」

Sonic hedgehog
	; 3D structure of the signaling domain of the murine Sonic hedgehog from PDB 1vhh
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	3HO5, 3M1N, 3MXW
Identifiers
Symbols	SHH; HHG1; HLP3; HPE3; MCOPCB5; SMMCI; TPT; TPTPS
External IDs	OMIM: 600725 MGI: 98297 HomoloGene: 30961 ChEMBL: 5602 GeneCards: SHH Gene
Gene Ontology
Molecular function	• glycoprotein binding; • signal transducer activity; • patched binding; • calcium ion binding; • protein binding; • glycosaminoglycan binding; • peptidase activity; • zinc ion binding; • morphogen activity; • laminin-1 binding;
Cellular component	• extracellular space; • nucleus; • endoplasmic reticulum; • Golgi apparatus; • plasma membrane; • cell surface; • transport vesicle; • extracellular matrix; • membrane raft;
Biological process	• negative regulation of transcription from RNA polymerase II promoter; • patterning of blood vessels; • vasculogenesis; • metanephros development; • branching involved in ureteric bud morphogenesis; • response to hypoxia; • cell fate specification; • neural crest cell migration; • neural tube formation; • heart looping; • positive regulation of neuroblast proliferation; • osteoblast development; • lymphoid progenitor cell differentiation; • determination of left/right asymmetry in lateral mesoderm; • proteolysis; • endocytosis; • apoptotic process; • smoothened signaling pathway; • positive regulation of hh target transcription factor activity; • cell-cell signaling; • pattern specification process; • ectoderm development; • neuroblast proliferation; • axon guidance; • central nervous system development; • ventral midline development; • hindgut morphogenesis; • digestive tract mesoderm development; • heart development; • blood coagulation; • androgen metabolic process; • positive regulation of cell proliferation; • embryo development; • embryonic pattern specification; • anterior/posterior pattern specification; • dorsal/ventral pattern formation; • response to organic nitrogen; • oligodendrocyte development; • positive regulation of skeletal muscle cell proliferation; • myotube differentiation; • intein-mediated protein splicing; • ventral spinal cord interneuron specification; • dorsal/ventral neural tube patterning; • smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation; • telencephalon regionalization; • establishment of cell polarity; • regulation of proteolysis; • positive regulation of Wnt receptor signaling pathway; • lung development; • embryonic limb morphogenesis; • negative regulation of cell migration; • male genitalia development; • prostate gland development; • regulation of epithelial cell differentiation; • thyroid gland development; • forebrain development; • midbrain development; • hindbrain development; • pancreas development; • hair follicle morphogenesis; • response to estradiol stimulus; • negative regulation of proteasomal ubiquitin-dependent protein catabolic process; • response to retinoic acid; • regulation of protein localization; • T cell differentiation in thymus; • positive regulation of T cell differentiation in thymus; • positive regulation of immature T cell proliferation in thymus; • negative regulation of transcription elongation from RNA polymerase II promoter; • protein localization to nucleus; • embryonic forelimb morphogenesis; • embryonic hindlimb morphogenesis; • regulation of cell proliferation; • negative regulation of T cell proliferation; • positive regulation of protein import into nucleus; • odontogenesis of dentin-containing tooth; • embryonic digit morphogenesis; • camera-type eye development; • negative regulation of apoptotic process; • CD4-positive or CD8-positive, alpha-beta T cell lineage commitment; • tongue morphogenesis; • skin development; • positive thymic T cell selection; • negative thymic T cell selection; • intermediate filament organization; • myoblast differentiation; • response to ethanol; • negative regulation of cell differentiation; • positive regulation of smoothened signaling pathway; • positive regulation of transcription, DNA-dependent; • positive regulation of transcription from RNA polymerase II promoter; • positive regulation of photoreceptor cell differentiation; • positive regulation of alpha-beta T cell differentiation; • negative regulation of alpha-beta T cell differentiation; • cell development; • thymus development; • embryonic digestive tract morphogenesis; • embryonic foregut morphogenesis; • positive regulation of skeletal muscle tissue development; • organ formation; • neuron fate commitment; • response to axon injury; • embryonic skeletal system development; • positive regulation of oligodendrocyte differentiation; • branching morphogenesis of a tube; • male genitalia morphogenesis; • inner ear development; • formation of anatomical boundary; • stem cell development; • positive regulation of striated muscle cell differentiation; • positive regulation of cell division; • Bergmann glial cell differentiation; • palate development; • canonical Wnt receptor signaling pathway; • limb bud formation; • positive regulation of penile erection; • lung epithelium development; • trachea morphogenesis; • branching involved in salivary gland morphogenesis; • bud outgrowth involved in lung branching; • right lung development; • left lung development; • lung lobe morphogenesis; • lung-associated mesenchyme development; • primary prostatic bud elongation; • prostate epithelial cord elongation; • salivary gland cavitation; • epithelial cell proliferation involved in salivary gland morphogenesis; • regulation of prostatic bud formation; • epithelial-mesenchymal signaling involved in prostate gland development; • positive regulation of epithelial cell proliferation involved in prostate gland development; • regulation of mesenchymal cell proliferation involved in prostate gland development; • mesenchymal smoothened signaling pathway involved in prostate gland development; • artery development; • mesenchymal cell proliferation involved in lung development; • somite development; • positive regulation of sclerotome development; • positive regulation of oligodendrocyte progenitor proliferation; • cellular response to lithium ion; • renal system development; • metanephric mesenchymal cell proliferation involved in metanephros development; • multicellular structure septum development; • negative regulation of canonical Wnt receptor signaling pathway; • negative regulation of cholesterol efflux; • regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry; • negative regulation of ureter smooth muscle cell differentiation; • positive regulation of ureter smooth muscle cell differentiation; • negative regulation of kidney smooth muscle cell differentiation; • positive regulation of kidney smooth muscle cell differentiation; • positive regulation of mesenchymal cell proliferation involved in ureter development;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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　　[★]

英: sonic hedgehog、Shh

「hedgehog」

　　[★] ハリネズミ、ヘッジホッグ

関: Erinaceidae

[1] なお、上述のゲーム作品「ソニックシリーズ」には、ナックルズ・ザ・エキドゥナというハリモグラのキャラクターも登場する。

[1] Anwood, Robert (2007-09-06). Emus Can't Walk Backwards. Ebury Press. pp. 113–114. ISBN 978-0-09-192151-4.

[url_zfin.org_shh_a-2] "Zebrafish shha". zfin.org. http://zfin.org/cgi-bin/webdriver?MIval=aa-markerview.apg&OID=ZDB-GENE-980526-166.

[url_zfin.org_shh_b-3] "Zebrafish shhb". zfin.org. http://zfin.org/cgi-bin/webdriver?MIval=aa-markerview.apg&OID=ZDB-GENE-980526-41.

[url_zfin.org_indian_hedgehog_b-4] "Zebrafish ihhb". zfin.org. http://zfin.org/cgi-bin/webdriver?MIval=aa-markerview.apg&OID=ZDB-GENE-980526-135.

[Currie-5] Currie P.D. and Ingham P.W. (1996). "Induction of a specific muscle cell type by a hedgehog-like protein in zebrafish". Nature 382 (6590): 452–5. doi:10.1038/382452a0. PMID 8684485.

[Herzog-6] Herzog W, Zeng X, Lele Z, Sonntag C, Ting JW, Chang CY, Hammerschmidt M (February 2003). "Adenohypophysis formation in the zebrafish and its dependence on sonic hedgehog". Dev. Biol. 254 (1): 36–49. doi:10.1016/S0012-1606(02)00124-0. PMID 12606280.

[Lewis-7] Lewis KE, Eisen JS (September 2001). "Hedgehog signaling is required for primary motoneuron induction in zebrafish". Development 128 (18): 3485–95. PMID 11566854.

[Scholpp-8] Scholpp S, Wolf O, Brand M, Lumsden A (March 2006). "Hedgehog signalling from the zona limitans intrathalamica orchestrates patterning of the zebrafish diencephalon". Development 133 (5): 855–64. doi:10.1242/dev.02248. PMID 16452095.

[Dassule-9] Dassule HR, Lewis P, Bei M, Maas R, McMahon AP (November 2000). "Sonic hedgehog regulates growth and morphogenesis of the tooth". Development 127 (22): 4775–85. PMID 11044393. http://dev.biologists.org/cgi/reprint/127/22/4775.pdf.

[Charron-10] Charron F, Stein E, Jeong J, McMahon AP, Tessier-Lavigne M (April 2003). "The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance". Cell 113 (1): 11–23. doi:10.1016/S0092-8674(03)00199-5. PMID 12679031.

[Kolpak-11] Kolpak A, Zhang J, Bao ZZ (March 2005). "Sonic hedgehog has a dual effect on the growth of retinal ganglion axons depending on its concentration". J. Neurosci. 25 (13): 3432–41. doi:10.1523/JNEUROSCI.4938-04.2005. PMC 1564194. PMID 15800198. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1564194/.

[Thewissen-12] Thewissen JG, Cohn MJ, Stevens LS, Bajpai S, Heyning J, Horton WE (May 2006). "Developmental basis for hind-limb loss in dolphins and origin of the cetacean bodyplan". Proc. Natl. Acad. Sci. U.S.A. 103 (22): 8414–8. doi:10.1073/pnas.0602920103. PMC 1482506. PMID 16717186. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1482506/.

[pmid11002335-13] Litingtung Y, Chiang C (October 2000). "Control of Shh activity and signaling in the neural tube". Dev. Dyn. 219 (2): 143–54. doi:10.1002/1097-0177(2000)9999:9999<::AID-DVDY1050>3.0.CO;2-Q. PMID 11002335.

[pmid7580143-14] Placzek M (August 1995). "The role of the notochord and floor plate in inductive interactions". Curr. Opin. Genet. Dev. 5 (4): 499–506. doi:10.1016/0959-437X(95)90055-L. PMID 7580143.

[pmid9751734-15] Teillet MA, Lapointe F, Le Douarin NM. (September 1998). "The relationships between notochord and floor plate in vertebrate development revisited.". roc Natl Acad Sci U S A. 95 (20): 11733–8. doi:10.1073/pnas.95.20.11733. PMID 9751734.

[pmid3834777-16] van Straaten HW, Hekking JW, Thors F, Wiertz-Hoessels EL, Drukker J (October 1985). "Induction of an additional floor plate in the neural tube". Acta Morphol Neerl Scand 23 (2): 91–7. PMID 3834777.

[17] I. Patten and M. Placzek (2000). CELLULAR AND MOLECULAR LIFE SCIENCES. 57. pp. 1695–1708. doi:10.1007/PL00000652.

[pmid7753196-18] Martí E, Bumcrot DA, Takada R, McMahon AP. (May 1995). "Requirement of 19K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explants.". Nature 375 (6529): 322–325. doi:10.1038/375322a0. PMID 7753196.

[pmid8929535-19] Ericson J, Morton S, Kawakami A, Roelink H, Jessell TM (November 1996). "Two critical periods of Sonic Hedgehog signaling required for the specification of motor neuron identity". Cell 87 (4): 661–73. doi:10.1016/S0092-8674(00)81386-0. PMID 8929535.

[pmid8837770-20] Chiang C, Litingtung Y, Lee E, Young KE, Corden JL, Westphal H, Beachy PA (October 1996). "Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function". Nature 383 (6599): 407–13. doi:10.1038/383407a0. PMID 8837770.

[pmid2237443-21] Placzek M, Tessier-Lavigne M, Yamada T, Jessell T, Dodd J (November 1990). "Mesodermal control of neural cell identity: floor plate induction by the notochord". Science 250 (4983): 985–8. doi:10.1126/science.2237443. PMID 2237443.

[pmid15936325-22] Wilson L, Maden M (June 2005). "The mechanisms of dorsoventral patterning in the vertebrate neural tube". Dev. Biol. 282 (1): 1–13. doi:10.1016/j.ydbio.2005.02.027. PMID 15936325.

[pmid8906787-23] Stone DM, Hynes M, Armanini M, Swanson TA, Gu Q, Johnson RL, Scott MP, Pennica D, Goddard A, Phillips H, Noll M, Hooper JE, de Sauvage F, Rosenthal A. (November 1996). "The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog.". Nature. 384 (6605): 129–34. doi:10.1038/384129a0. PMID 8906787.

[pmid8790332-24] Marigo V, Tabin CJ (September 1996). "Regulation of patched by sonic hedgehog in the developing neural tube". Proc. Natl. Acad. Sci. U.S.A. 93 (18): 9346–51. doi:10.1073/pnas.93.18.9346. PMC 38430. PMID 8790332. //www.ncbi.nlm.nih.gov/pmc/articles/PMC38430/.

[pmid9598380-25] Ericson J, Briscoe J, Rashbass P, van Heyningen V, Jessell TM. (1997). "Graded sonic hedgehog signaling and the specification of cell fate in the ventral neural tube.". Cold Spring Harb Symp Quant Biol. 62: 451–66. doi:10.1101/SQB.1997.062.01.053. PMID 9598380.

[pmid9230312-26] Ericson J, Rashbass P, Schedl A, Brenner-Morton S, Kawakami A, van Heyningen V, Jessell TM, Briscoe J. (July 1997). "Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling.". Cell 90 (1): 169–80. doi:10.1016/S0092-8674(00)80323-2. PMID 9230312.

[pmid15205520-27] Lum L, Beachy PA. (June 2004). "The Hedgehog response network: sensors, switches, and routers.". Science 304: 1755–9. doi:10.1126/science.1098020. PMID 15205520.

[pmid9584120-28] Ruiz i Altaba A. (June 1998). "Combinatorial Gli gene function in floor plate and neuronal inductions by Sonic hedgehog.". Development 125 (12): 2203–12. PMID 9584120. http://dev.biologists.org/content/125/12/2203.long.

[pmid10725236-29] Park HL, Bai C, Platt KA, Matise MP, Beeghly A, Hui CC, Nakashima M, Joyner AL. (April 2000). "Mouse Gli1 mutants are viable but have defects in SHH signaling in combination with a Gli2 mutation.". Development 127 (8): 1593–605. PMID 10725236. http://dev.biologists.org/content/127/8/1593.long.

[pmid9655799-30] Matise MP, Epstein DJ, Park HL, Platt KA, Joyner AL. (August 1998). "Gli2 is required for induction of floor plate and adjacent cells, but not most ventral neurons in the mouse central nervous system.". Development 125 (15): 2759–70. PMID 9655799. http://dev.biologists.org/content/125/15/2759.long.

[pmid11017169-31] Litingtung Y, Chiang C. (October 2000). "Specification of ventral neuron types is mediated by an antagonistic interaction between Shh and Gli3.". Nat Neurosci 3 (10): 979–85. doi:10.1038/79916. PMID 11017169.

[pmid10433919-32] Sasaki H, Nishizaki Y, Hui C, Nakafuku M, Kondoh H. (September 1999). "Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: implication of Gli2 and Gli3 as primary mediators of Shh signaling.". Development 126 (17): 3915–24. PMID 10433919. http://dev.biologists.org/content/126/17/3915.long.

[pmid12435629-33] Persson M, Stamataki D, te Welscher P, Andersson E, Böse J, Rüther U, Ericson J, Briscoe J. (November 2002). "Dorsal-ventral patterning of the spinal cord requires Gli3 transcriptional repressor activity.". Genes Dev 16 (22): 2865–78. doi:10.1101/gad.243402. PMID 12435629.

[pmid10050855-34] Chuang PT, McMahon AP. (February 1999). "Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein.". Nature 397: 617–21. doi:10.1038/17611. PMID 10050855.

[pmid10603350-35] Pons S, Martí E. (January 2000). "Sonic hedgehog synergizes with the extracellular matrix protein vitronectin to induce spinal motor neuron differentiation.". Development 127 (2): 333–42. PMID 10603350. http://dev.biologists.org/content/127/2/333.long.

[pmid10830170-36] Briscoe J, Pierani A, Jessell TM, Ericson J. (May 2000). "A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube.". Cell 101 (4): 435–45. doi:10.1016/S0092-8674(00)80853-3. PMID 10830170.

[pmid11044400-37] Liem KF Jr, Jessell TM, Briscoe J. (November 2000). "Regulation of the neural patterning activity of sonic hedgehog by secreted BMP inhibitors expressed by notochord and somites.". Development 127 (22): 4855–66. PMID 11044400. http://dev.biologists.org/content/127/22/4855.long.

[pmid9585504-38] McMahon JA, Takada S, Zimmerman LB, Fan CM, Harland RM, McMahon AP. (May 1998). "Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite.". Genes Dev 12 (10): 1438–52. doi:10.1101/gad.12.10.1438. PMC 316831. PMID 9585504. //www.ncbi.nlm.nih.gov/pmc/articles/PMC316831/.

[Roelink-39] Roelink H, Porter JA, Chiang C, Tanabe Y, Chang DT, Beachy PA, Jessel TM (May 1995). "Floor Plate and Motor Neuron Induction by Different Concentrations of the Amino-Terminal Cleavage Product of Sonic Hedgehog Autoproteolysis". Cell 81 (3): 445–455. doi:10.1016/0092-8674(95)90397-6. PMID 7736596.

[Ribes-40] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j Ribes V, Briscoe J (August 2009). "Establishing and interpreting Graded Sonic Hedgehog during Vertebrate Neural Tube Patterning: The Role of Negative Feedback". Cold Spring Harb Perspect Biol 1(2): a002014 (2): a002014. doi:10.1101/cshperspect.a002014. PMC 2742090. PMID 20066087. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2742090/.

[Chamberlain-41] Chamberlain CE, Jeong J, Guo C, Allen BL, McMahon AP (March 2008). "Notochord-derived Shh concentrates in close association with the apically positioned basal body in neural target cells and forms a dynamic gradient during neural patterning". Development 135 (6): 1097–1106. doi:10.1242/dev.013086. PMID 18272593.

[Bumcrot-42] Bumcrot DA, Takada R and McMahon AP (1 April 1995). "Proteolytic processing yields two secreted forms of sonic hedgehog". Mol Cell Biol. 15 (4): 2294–2303. PMC 230457. PMID 7891723. //www.ncbi.nlm.nih.gov/pmc/articles/PMC230457/.

[Porter-43] Porter JA, Young KE and Beachy PA (1996). "Cholesterol modification of hedgehog signaling proteins in animal development". Science 274 (5285): 255–259. doi:10.1126/science.274.5285.255. PMID 8824192.

[Pepinsky-44] Pepinsky RB, Zeng C, Wen D, Rayhorn P, Baker DP, Williams KP, Bixler SA, Ambrose CM, Garber EA, Miatkowski K et al. (1998). "Identification of a palmitic acid-modified form of human Sonic hedgehog". J Biol Chem 273 (22): 14037–14045. doi:10.1074/jbc.273.22.14037. PMID 9593755. http://www.jbc.org/cgi/content/full/273/22/14037.

[pmid16421543-45] Maclean K (January 2006). "Humour of gene names lost in translation to patients". Nature 439 (7074): 266. doi:10.1038/439266d. PMID 16421543.

[pmid16718675-46] Cohen MM (July 2006). "Problems in the naming of genes". Am. J. Med. Genet. A 140 (13): 1483–4. doi:10.1002/ajmg.a.31264. PMID 16718675.

匿名

検索

案内

案内

sonic hedgehog