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Sonic hedgehog protein – Wikipedia

by
January 27, 2023
2023-01-26 15:06:49

Signaling molecule in animals

SHH
Shh structure.png
Identifiers
Aliases SHH, HHG1, HLP3, HPE3, MCOPCB5, SMMCI, TPT, TPTPS, sonic hedgehog, Sonic hedgehog, ShhNC, sonic hedgehog signaling molecule
Exterior IDs OMIM: 600725 MGI: 98297 HomoloGene: 30961 GeneCards: SHH
Wikidata

Sonic hedgehog protein (SHH) is encoded for by the SHH gene.[5] The protein is known as after the character Sonic the Hedgehog.

This signaling molecule is vital in regulating embryonic morphogenesis in all animals. SHH controls organogenesis and the group of the central nervous system, limbs, digits and lots of different components of the physique. Sonic hedgehog is a morphogen that patterns the creating embryo utilizing a focus gradient characterised by the French flag model.[6] This mannequin has a non-uniform distribution of SHH molecules which governs totally different cell fates in response to focus. Mutations on this gene may cause holoprosencephaly, a failure of splitting within the cerebral hemispheres,[7] as demonstrated in an experiment utilizing SHH knock-out mice by which the forebrain midline didn’t develop and as a substitute solely a single fused telencephalic vesicle resulted.[8]

Sonic hedgehog nonetheless performs a job in differentiation, proliferation, and upkeep of grownup tissues. Irregular activation of SHH signaling in grownup tissues has been implicated in numerous forms of cancers together with breast, skin, brain, liver, gallbladder and lots of extra.[9]

Discovery and naming[edit]

The hedgehog gene (hh) was first recognized within the fruit fly Drosophila melanogaster within the traditional Heidelberg screens of Christiane Nüsslein-Volhard and Eric Wieschaus, as revealed in 1980.[10] These screens, which led to the researchers successful a Nobel Prize in 1995 together with developmental geneticist Edward B. Lewis, recognized genes that management the segmentation sample of the Drosophila embryos. The hh lack of perform mutant phenotype causes the embryos to be coated with denticles, i.e. small pointy projections resembling the spikes of a hedgehog. Investigations geared toward discovering a hedgehog equal in vertebrates by Philip Ingham, Andrew P. McMahon and Clifford Tabin revealed three homologous genes.[11][12][13][14]

Two of those genes, desert hedgehog and Indian hedgehog, have been named for species of hedgehogs, whereas sonic hedgehog was named after the online game character Sonic the Hedgehog.[15][16] The gene was named by Robert Riddle, a postdoctoral fellow on the Tabin Lab, after his spouse Betsy Wilder got here residence with {a magazine} containing an advert for the sport Sonic the Hedgehog.[17][18][19] Within the zebrafish, two of the three vertebrate hh genes are duplicated: SHH a[20] and SHH b[21] (previously described as tiggywinkle hedgehog, named for Mrs. Tiggy-Winkle, a personality from Beatrix Potter‘s books for kids) and ihha and ihhb[22] (previously described as echidna hedgehog, named for the spiny anteater and never for the character Knuckles the Echidna within the Sonic franchise).

Operate[edit]

Of the hh homologues, SHH has been discovered to have probably the most vital roles in growth, performing as a morphogen concerned in patterning many methods—together with the anterior pituitary,[23] pallium of the mind,[24] spinal cord,[25] lungs,[26] enamel[27] and the thalamus by the zona limitans intrathalamica.[28][29] In vertebrates, the development of limbs and digits will depend on the secretion of sonic hedgehog by the zone of polarizing activity, situated on the posterior facet of the embryonic limb bud.[13] Mutations within the human sonic hedgehog gene SHH trigger holoprosencephaly sort 3 HPE3, because of the lack of the ventral midline. The sonic hedgehog transcription pathway has additionally been linked to the formation of particular sorts of cancerous tumors, together with the embryonic cerebellar tumor[30] and medulloblastoma,[31] in addition to the development of prostate cancer tumours.[32] For SHH to be expressed within the creating embryo limbs, a morphogen referred to as fibroblast growth factors have to be secreted from the apical ectodermal ridge.[33]

Sonic hedgehog has additionally been proven to behave as an axonal guidance cue. It has been demonstrated that SHH attracts commissural axons on the ventral midline of the creating spinal twine.[34] Particularly, SHH attracts retinal ganglion cell (RGC) axons at low concentrations and repels them at greater concentrations.[35] The absence (non-expression) of SHH has been proven to regulate the expansion of nascent hind limbs in cetaceans[36] (whales and dolphins).

The SHH gene is a member of the hedgehog gene household with 5 variations of DNA sequence alterations or splice variants.[37] SHH is situated on chromosome seven and initiates the manufacturing of Sonic Hedgehog protein.[37] This protein sends short- and long-range indicators to embryonic tissues to manage growth.[38] If the SHH gene is mutated or absent, the protein Sonic Hedgehog can not do its job correctly. Sonic hedgehog contributes to cell development, cell specification and formation, structuring and group of the physique plan.[39] This protein capabilities as a significant morphogenic signaling molecule and performs an essential function within the formation of many various buildings in creating embryos.[39] The SHH gene impacts a number of main organ methods, such because the nervous system, cardiovascular system, respiratory system and musculoskeletal system.[37][38] Mutations within the SHH gene may cause malformation of parts of those methods, which can lead to main issues within the creating embryo. The mind and eyes, for instance, may be considerably impacted by mutations on this gene and trigger issues comparable to Microphthalmia and Holoprosencephaly.[39] Microphthalmia is a situation that impacts the eyes, which leads to small, underdeveloped tissues in a single or each eyes.[39] This could result in points starting from a coloboma to a single small eye to the absence of eyes altogether.[38] Holoprosencephaly is a situation mostly brought on by a mutation of the SHH gene that causes improper separation of the left and proper mind and facial dysmorphia.[38][39] Many methods and buildings rely closely on correct expression of the SHH gene and subsequent sonic hedgehog protein, incomes it the excellence of being an important gene to growth.

Patterning of the central nervous system[edit]

The sonic hedgehog (SHH) signaling molecule assumes numerous roles in patterning the central nervous system (CNS) throughout vertebrate development. One of the vital characterised capabilities of SHH is its function within the induction of the floor plate and various ventral cell sorts throughout the neural tube.[40] The notochord—a construction derived from the axial mesoderm—produces SHH, which travels extracellularly to the ventral area of the neural tube and instructs these cells to type the ground plate.[41] One other view of flooring plate induction hypothesizes that some precursor cells situated within the notochord are inserted into the neural plate earlier than its formation, later giving rise to the ground plate.[42]

The neural tube itself is the preliminary groundwork of the vertebrate CNS, and the floor plate is a specialised construction, situated on the ventral midpoint of the neural tube. Proof supporting the notochord because the signaling heart comes from research by which a second notochord is implanted close to a neural tube in vivo, resulting in the formation of an ectopic flooring plate throughout the neural tube.[43]

  • morphogens that pattern the dorsoventral axes of the neural tube

    SHH and BMP gradients within the vertebrate neural tube

  • Depiction of the formation of an ectopic floor plate within the neural tube in the presence of a second notochord

    Ectopic flooring plate formation

  • Depiction of domains of the ventral neuronal cell types in the neural tube

    Ventral neural domains in neural tube

Sonic hedgehog is the secreted protein that mediates signaling actions of the notochord and flooring plate.[44] Research involving ectopic expression of SHH in vitro[45] and in vivo[46] end in flooring plate induction and differentiation of motor neuron and ventral interneurons. Then again, mice mutants for SHH lack ventral spinal twine traits.[47] In vitro blocking of SHH signaling utilizing antibodies in opposition to it reveals related phenotypes.[46] SHH exerts its results in a concentration-dependent method,[48] so {that a} excessive focus of SHH ends in an area inhibition of cellular proliferation.[49] This inhibition causes the ground plate to turn into skinny in comparison with the lateral areas of the neural tube. Decrease focus of SHH ends in mobile proliferation and induction of varied ventral neural cell sorts.[46] As soon as the floor plate is established, cells residing on this area will subsequently categorical SHH themselves,[49] producing a concentration gradient throughout the neural tube.

Though there isn’t a direct proof of a SHH gradient, there’s oblique proof by way of the visualization of Patched (Ptc) gene expression, which encodes for the ligand binding area of the SHH receptor[50] all through the ventral neural tube.[51] In vitro research present that incremental two- and threefold modifications in SHH focus give rise to motor neuron and totally different interneuronal subtypes as discovered within the ventral spinal twine.[52] These incremental modifications in vitro correspond to the gap of domains from the signaling tissue (notochord and flooring plate) which subsequently differentiates into totally different neuronal subtypes because it happens in vitro.[53] Graded SHH signaling is usually recommended to be mediated by means of the Gli household of proteins, that are vertebrate homologues of the Drosophila zinc-finger-containing transcription factor Cubitus interruptus (Ci). Ci is an important mediator of hedgehog (Hh) signaling in Drosophila.[54] In vertebrates, three totally different Gli proteins are current, viz. Gli1, Gli2 and Gli3, that are expressed within the neural tube.[55] Mice mutants for Gli1 present regular spinal twine growth, suggesting that it’s dispensable for mediating SHH exercise.[56] Nonetheless, Gli2 mutant mice present abnormalities within the ventral spinal twine, with extreme defects within the flooring plate and ventral-most interneurons (V3).[57] Gli3 antagonizes SHH perform in a dose-dependent method, selling dorsal neuronal subtypes. SHH mutant phenotypes may be rescued in a SHH/Gli3 double mutant.[58] Gli proteins have a C-terminal activation area and an N-terminal repressive area.[55][59]

SHH is usually recommended to advertise the activation perform of Gli2 and inhibit repressive exercise of Gli3. SHH additionally appears to advertise the activation perform of Gli3, however this exercise isn’t robust sufficient.[58] The graded focus of SHH offers rise to graded exercise of Gli 2 and Gli3, which promote ventral and dorsal neuronal subtypes within the ventral spinal twine. Proof from Gli3 and SHH/Gli3 mutants present that SHH primarily regulates the spatial restriction of progenitor domains fairly than being inductive, as SHH/Gli3 mutants present intermixing of cell sorts.[58][60]

SHH additionally induces different proteins with which it interacts, and these interactions can affect the sensitivity of a cell in the direction of SHH. Hedgehog-interacting protein (HHIP) is induced by SHH, which in flip attenuates its signaling exercise.[61] Vitronectin is one other protein that’s induced by SHH; it acts as an obligate co-factor for SHH signaling within the neural tube.[62]

There are 5 distinct progenitor domains within the ventral neural tube: V3 interneurons, motor neurons (MN), V2, V1, and V0 interneurons (in ventral to dorsal order).[52] These totally different progenitor domains are established by “communication” between totally different courses of homeobox transcription factors. (See Trigeminal Nerve.) These transcription factors reply to SHH gradient focus. Relying upon the character of their interplay with SHH, they’re labeled into two teams—class I and sophistication II—and are composed of members from the Pax, Nkx, Dbx and Irx households.[49] Class I proteins are repressed at totally different thresholds of SHH delineating ventral boundaries of progenitor domains, whereas class II proteins are activated at totally different thresholds of SHH delineating the dorsal restrict of domains. Selective cross-repressive interactions between class I and sophistication II proteins give rise to 5 cardinal ventral neuronal subtypes.[63]

It is very important notice that SHH isn’t the one signaling molecule exerting an impact on the creating neural tube. Many different molecules, pathways and mechanisms are lively (e.g., RA, FGF, BMP), and sophisticated interactions between SHH and different molecules are potential. BMPs are urged to play a vital function in figuring out the sensitivity of neural cell to SHH signaling. Proof supporting this comes from research utilizing BMP inhibitors that ventralize the destiny of the neural plate cell for a given SHH focus.[64] Then again, mutation in BMP antagonists (e.g., noggin) produces extreme defects within the ventral-most traits of the spinal twine, adopted by ectopic expression of BMP within the ventral neural tube.[65] Interactions of SHH with Fgf and RA haven’t but been studied in molecular element.

Morphogenetic exercise[edit]

The concentration- and time-dependent, cell-fate-determining exercise of SHH within the ventral neural tube makes it a first-rate instance of a morphogen. In vertebrates, SHH signaling within the ventral portion of the neural tube is most notably chargeable for the induction of floor plate cells and motor neurons.[66] SHH emanates from the notochord and ventral flooring plate of the creating neural tube to create a concentration gradient that spans the dorso-ventral axis and is antagonized by an inverse Wnt gradient, which specifies the dorsal spinal chord.[67][68] Greater concentrations of the SHH ligand are present in probably the most ventral features of the neural tube and notochord, whereas decrease concentrations are discovered within the extra dorsal areas of the neural tube.[67] The SHH focus gradient has been visualized within the neural tube of mice engineered to precise a SHH::GFP fusion protein to indicate this graded distribution of SHH through the time of ventral neural tube patterning.[69]

It’s thought that the SHH gradient works to elicit a number of totally different cell fates by a concentration- and time-dependent mechanism that induces quite a lot of transcription elements within the ventral progenitor cells.[67][69] Every of the ventral progenitor domains expresses a extremely individualized mixture of transcription elements—Nkx2.2, Olig2, Nkx6.1, Nkx6.2, Dbx1, Dbx2, Irx3, Pax6, and Pax7—that’s regulated by the SHH gradient. These transcription elements are induced sequentially alongside the SHH focus gradient with respect to the quantity and time of publicity to SHH ligand.[67] As every inhabitants of progenitor cells responds to the totally different ranges of SHH protein, they start to precise a singular mixture of transcription elements that results in neuronal cell destiny differentiation. This SHH-induced differential gene expression creates sharp boundaries between the discrete domains of transcription issue expression, which finally patterns the ventral neural tube.[67]

The spatial and temporal side of the progressive induction of genes and cell fates within the ventral neural tube is illustrated by the expression domains of two of probably the most well-characterized transcription elements, Olig2 and Nkx2.2.[67] Early in growth, the cells on the ventral midline have solely been uncovered to a low focus of SHH for a comparatively brief time and categorical the transcription issue Olig2.[67] The expression of Olig2 quickly expands in a dorsal path concomitantly with the continual dorsal extension of the SHH gradient over time.[67] Nonetheless, because the morphogenetic entrance of SHH ligand strikes and begins to develop extra concentrated, cells which might be uncovered to greater ranges of the ligand reply by switching off Olig2 and turning on Nkx2.2,[67] creating a pointy boundary between the cells expressing the transcription issue Nkx2.2 ventral to the cells expressing Olig2. It’s on this method that every of the domains of the six progenitor cell populations are considered successively patterned all through the neural tube by the SHH focus gradient.[67] Mutual inhibition between pairs of transcription elements expressed in neighboring domains contributes to the event of sharp boundaries; nevertheless, in some instances, inhibitory relationship has been discovered even between pairs of transcription elements from extra distant domains. Significantly, NKX2-2 expressed within the V3 area is reported to inhibit IRX3 expressed in V2 and extra dorsal domains, though V3 and V2 are separated by an extra area termed MN.[70]

See Also
Launch Paperless-ngx v2.0.0 · paperless-ngx/paperless-ngx · GitHub

SHH expression within the frontonasal ectodermal zone (FEZ), which is a signaling heart that’s chargeable for the patterned growth of the higher jaw, regulates craniofacial growth mediating by means of the miR-199 household within the FEZ. Particularly, SHH-dependent indicators from the mind regulate genes of the miR-199 household with downregulations of the miR-199 genes growing SHH expression and leading to wider faces, whereas upregulations of the miR-199 genes lower SHH expression leading to slender faces.[71]

Tooth growth[edit]

SHH performs a vital function in organogenesis and, most significantly, craniofacial growth. Being that SHH is a signaling molecule, it primarily works by diffusion alongside a focus gradient, affecting cells in numerous manners. In early tooth growth, SHH is launched from the first enamel knot—a signaling heart—to offer positional data in each a lateral and planar signaling sample in tooth growth and regulation of tooth cusp development.[72] SHH specifically is required for development of epithelial cervical loops, the place the outer and inside epitheliums be part of and type a reservoir for dental stem cells. After the first enamel knots are apoptosed, the secondary enamel knots are fashioned. The secondary enamel knots secrete SHH together with different signaling molecules to thicken the oral ectoderm and start patterning the complicated shapes of the crown of a tooth throughout differentiation and mineralization.[73] In a knockout gene mannequin, absence of SHH is indicative of holoprosencephaly. Nonetheless, SHH prompts downstream molecules of Gli2 and Gli3. Mutant Gli2 and Gli3 embryos have irregular growth of incisors which might be arrested in early tooth growth in addition to small molars.[74]

Lung growth[edit]

Though SHH is mostly related to mind and limb digit growth, it’s also essential in lung growth.[75][76][77][78] Research utilizing qPCR and knockouts have demonstrated that SHH contributes to embryonic lung growth. The mammalian lung branching happens within the epithelium of the creating bronchi and lungs.[79][80] SHH expressed all through the foregut endoderm (innermost of three germ layers) within the distal epithelium, the place the embryonic lungs are creating.[77][80] This means that SHH is partially chargeable for the branching of the lungs. Additional proof of SHH’s function in lung branching has been seen with qPCR. SHH expression happens within the creating lungs round embryonic day 11 and is strongly expressed within the buds of the fetal lungs however low within the creating bronchi.[77][80] Mice who’re poor in SHH can develop tracheoesophageal fistula (irregular connection of the esophagus and trachea).[81][77] Moreover, a double (SHH-/- ) knockout mouse mannequin exhibited poor lung growth. The lungs of the SHH double knockout didn’t endure lobation and branching (i.e., the irregular lungs solely developed one department, in comparison with an extensively branched phenotype of the wildtype).[77]

Potential regenerative perform[edit]

Sonic hedgehog could play a job in mammalian hair cell regeneration. By modulating retinoblastoma protein exercise in rat cochlea, sonic hedgehog permits mature hair cells that usually can not return to a proliferative state to divide and differentiate. Retinoblastoma proteins suppress cell development by stopping cells from returning to the cell cycle, thereby stopping proliferation. Inhibiting the exercise of Rb appears to permit cells to divide. Due to this fact, sonic hedgehog—recognized as an essential regulator of Rb—may additionally show to be an essential function in regrowing hair cells after injury.[82]

SHH is essential for regulating dermal adipogenesis by hair follicle transit-amplifying cells (HF-TACs). Particularly, SHH induces dermal angiogenesis by performing immediately on adipocyte precursors and selling their proliferation by means of their expression of the peroxisome proliferator-activated receptor γ (Pparg) gene.[83]

Processing[edit]

SHH undergoes a sequence of processing steps earlier than it’s secreted from the cell. Newly synthesised SHH weighs 45 kDa and is known as the preproprotein. As a secreted protein, it accommodates a brief signal sequence at its N-terminus, which is recognised by the signal recognition particle through the translocation into the endoplasmic reticulum (ER), step one in protein secretion. As soon as translocation is full, the sign sequence is eliminated by signal peptidase within the ER. There, SHH undergoes autoprocessing to generate a 20 kDa N-terminal signaling area (SHH-N) and a 25 kDa C-terminal area with no identified signaling function.[84] The cleavage is catalysed by a protease throughout the C-terminal area. Through the response, a cholesterol molecule is added to the C-terminus of SHH-N.[85][86] Thus, the C-terminal area acts as an intein and a ldl cholesterol transferase. One other hydrophobic moiety, a palmitate, is added to the alpha-amine of N-terminal cysteine of SHH-N. This modification is required for environment friendly signaling, leading to a 30-fold enhance in efficiency over the non-palmitylated type and is carried out by a member of the membrane-bound O-acyltransferase household Protein-cysteine N-palmitoyltransferase HHAT.[87]

Robotnikinin[edit]

A possible inhibitor of the Hedgehog signaling pathway has been discovered and dubbed “Robotnikinin”—in honour of Sonic the Hedgehog’s nemesis, Dr. Ivo “Eggman” Robotnik.[88]

Former controversy surrounding identify[edit]

The gene has been linked to a situation often called holoprosencephaly, which can lead to extreme mind, cranium and facial defects, inflicting a couple of clinicians and scientists to criticize the identify on the grounds that it sounds too frivolous. It has been famous that point out of a mutation in a sonic hedgehog gene may not be effectively obtained in a dialogue of a severe dysfunction with a affected person or their household.[17][89][90] This controversy has largely died down, and the identify is now typically seen as a humorous relic of the time earlier than the rise of quick, low cost full genome sequencing and standardized nomenclature.[91] The issue of the “inappropriateness” of the names of genes comparable to “Mothers against decapentaplegic“, “Lunatic fringe“, and “Sonic hedgehog” is essentially prevented through the use of standardized abbreviations when talking with sufferers and their households.[92]

Gallery[edit]

Interaction between SHH and Gli proteins which gives rise to different ventral neuronal subtypes.

SHH gradient and Gli exercise within the vertebrate neural tube.
Sonichedgehog.svg

See additionally[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000164690 – Ensembl, Might 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000002633 – Ensembl, Might 2017
  3. ^ “Human PubMed Reference:”. Nationwide Middle for Biotechnology Info, U.S. Nationwide Library of Medication.
  4. ^ “Mouse PubMed Reference:”. Nationwide Middle for Biotechnology Info, U.S. Nationwide Library of Medication.
  5. ^ Marigo V, Roberts DJ, Lee SM, Tsukurov O, Levi T, Gastier JM, et al. (July 1995). “Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila phase polarity gene hedgehog”. Genomics. 28 (1): 44–51. doi:10.1006/geno.1995.1104. PMID 7590746.
  6. ^ Jaeger J, Martinez-Arias A (March 2009). “Getting the measure of positional information”. PLOS Biology. 7 (3): e81. doi:10.1371/journal.pbio.1000081. PMC 2661971. PMID 19338391.
  7. ^ Nanni L, Ming JE, Bocian M, Steinhaus Okay, Bianchi DW, Die-Smulders C, et al. (December 1999). “The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations trigger a big proportion of autosomal dominant holoprosencephaly”. Human Molecular Genetics. 8 (13): 2479–2488. doi:10.1093/hmg/8.13.2479. PMID 10556296.
  8. ^ Blaess S, Szabó N, Haddad-Tóvolli R, Zhou X, Álvarez-Bolado G (2015-01-06). “Sonic hedgehog signaling in the development of the mouse hypothalamus”. Frontiers in Neuroanatomy. 8: 156. doi:10.3389/fnana.2014.00156. PMC 4285088. PMID 25610374.
  9. ^ Jeng KS, Chang CF, Lin SS (January 2020). “Sonic Hedgehog Signaling in Organogenesis, Tumors, and Tumor Microenvironments”. Worldwide Journal of Molecular Sciences. 21 (3): 758. doi:10.3390/ijms21030758. PMC 7037908. PMID 31979397.
  10. ^ Nüsslein-Volhard C, Wieschaus E (October 1980). “Mutations affecting phase quantity and polarity in Drosophila”. Nature. 287 (5785): 795–801. Bibcode:1980Natur.287..795N. doi:10.1038/287795a0. PMID 6776413. S2CID 4337658.
  11. ^ Krauss S, Concordet JP, Ingham PW (December 1993). “A functionally conserved homolog of the Drosophila phase polarity gene hh is expressed in tissues with polarizing exercise in zebrafish embryos”. Cell. 75 (7): 1431–1444. doi:10.1016/0092-8674(93)90628-4. PMID 8269519. S2CID 46266627.
  12. ^ Echelard Y, Epstein DJ, St-Jacques B, Shen L, Mohler J, McMahon JA, McMahon AP (December 1993). “Sonic hedgehog, a member of a household of putative signaling molecules, is implicated within the regulation of CNS polarity”. Cell. 75 (7): 1417–1430. doi:10.1016/0092-8674(93)90627-3. PMID 7916661. S2CID 6732599.
  13. ^ a b Riddle RD, Johnson RL, Laufer E, Tabin C (December 1993). “Sonic hedgehog mediates the polarizing exercise of the ZPA”. Cell. 75 (7): 1401–1416. doi:10.1016/0092-8674(93)90626-2. PMID 8269518. S2CID 4973500.
  14. ^ Angier N (1994-01-11). “Biologists Find Key Genes That Shape Patterning of Embryos”. The New York Occasions. Archived from the unique on 2017-08-17. Retrieved 2017-02-18.
  15. ^ Anwood R (2007-09-06). Emus Can’t Walk Backwards. Ebury Press. pp. 113–114. ISBN 978-0-09-192151-4. Archived from the unique on 2017-05-07. Retrieved 2016-10-06.
  16. ^ Simonite T (2005-12-15). “Pokémon blocks gene name”. Nature. 438 (897): 897. doi:10.1038/438897a. PMID 16355177. S2CID 37632823. Archived from the unique on 2010-10-31. Retrieved 2013-05-23.
  17. ^ a b “A Gene Named Sonic”. The New York Occasions. 1994-01-11. Archived from the unique on 2018-02-28. Retrieved 2017-02-18.
  18. ^ Eager A, Tabin C (April 12, 2004). “Cliff Tabin: Super Sonic An Interview”. The Weekly Murmur. Archived from the original on November 10, 2005. Retrieved April 24, 2014.
  19. ^ Riddle R. Ingenious: The Cyclops Gene. BBC.co.uk. Interviewed by Kat Arney. BBC Radio.
  20. ^ “Zebrafish SHHa”. College of Oregon. Archived from the original on 2009-06-25.
  21. ^ “Zebrafish SHHb”. College of Oregon. Archived from the original on 2009-06-26.
  22. ^ Currie PD, Ingham PW (August 1996). “Induction of a particular muscle cell sort by a hedgehog-like protein in zebrafish”. Nature. 382 (6590): 452–455. Bibcode:1996Natur.382..452C. doi:10.1038/382452a0. PMID 8684485. S2CID 4271898.
  23. ^ Herzog W, Zeng X, Lele Z, Sonntag C, Ting JW, Chang CY, Hammerschmidt M (February 2003). “Adenohypophysis formation within the zebrafish and its dependence on sonic hedgehog”. Developmental Biology. 254 (1): 36–49. doi:10.1016/S0012-1606(02)00124-0. PMID 12606280.
  24. ^ Rash BG, Grove EA (October 2007). “Patterning the dorsal telencephalon: a role for sonic hedgehog?”. The Journal of Neuroscience. 27 (43): 11595–11603. doi:10.1523/JNEUROSCI.3204-07.2007. PMC 6673221. PMID 17959802.
  25. ^ Lewis KE, Eisen JS (September 2001). “Hedgehog signaling is required for main motoneuron induction in zebrafish”. Improvement. 128 (18): 3485–3495. doi:10.1242/dev.128.18.3485. PMID 11566854.
  26. ^ Wolpert L (2015). Rules of Improvement (fifth ed.). Oxford College Press. p. 500.
  27. ^ Dassule HR, Lewis P, Bei M, Maas R, McMahon AP (November 2000). “Sonic hedgehog regulates development and morphogenesis of the tooth”. Improvement. 127 (22): 4775–4785. doi:10.1242/dev.127.22.4775. PMID 11044393.
  28. ^ Scholpp S, Wolf O, Model M, Lumsden A (March 2006). “Hedgehog signalling from the zona limitans intrathalamica orchestrates patterning of the zebrafish diencephalon”. Improvement. 133 (5): 855–864. doi:10.1242/dev.02248. PMID 16452095. S2CID 27550686.
  29. ^ Rash BG, Grove EA (November 2011). “Shh and Gli3 regulate formation of the telencephalic-diencephalic junction and suppress an isthmus-like signaling source in the forebrain”. Developmental Biology. 359 (2): 242–250. doi:10.1016/j.ydbio.2011.08.026. PMC 3213684. PMID 21925158.
  30. ^ Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, et al. (April 2012). “Molecular subgroups of medulloblastoma: the current consensus”. Acta Neuropathologica. 123 (4): 465–472. doi:10.1007/s00401-011-0922-z. PMC 3306779. PMID 22134537.
  31. ^ DeSouza RM, Jones BR, Lowis SP, Kurian KM (22 July 2014). “Pediatric medulloblastoma – update on molecular classification driving targeted therapies”. Frontiers in Oncology. 4: 176. doi:10.3389/fonc.2014.00176. PMC 4105823. PMID 25101241.
  32. ^ Lubik AA, Nouri M, Truong S, Ghaffari M, Adomat HH, Corey E, et al. (January 2017). “Paracrine sonic hedgehog signaling contributes considerably to acquired steroidogenesis within the prostate tumor microenvironment”. Worldwide Journal of Most cancers. 140 (2): 358–369. doi:10.1002/ijc.30450. PMID 27672740. S2CID 2354209.
  33. ^ Riddle RD, Tabin C (February 1999). “How limbs develop”. Scientific American. 280 (2): 74–79. Bibcode:1999SciAm.280b..74R. doi:10.1038/scientificamerican0299-74. PMID 9924814.
  34. ^ 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 steerage”. Cell. 113 (1): 11–23. doi:10.1016/S0092-8674(03)00199-5. PMID 12679031. S2CID 13909497.
  35. ^ 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”. The Journal of Neuroscience. 25 (13): 3432–3441. doi:10.1523/JNEUROSCI.4938-04.2005. PMC 1564194. PMID 15800198.
  36. ^ Thewissen JG, Cohn MJ, Stevens LS, Bajpai S, Heyning J, Horton WE (Might 2006). “Developmental basis for hind-limb loss in dolphins and origin of the cetacean bodyplan”. Proceedings of the Nationwide Academy of Sciences of america of America. 103 (22): 8414–8418. Bibcode:2006PNAS..103.8414T. doi:10.1073/pnas.0602920103. PMC 1482506. PMID 16717186.
  37. ^ a b c “ENSG00000164690”. GRCh38. Ensembl launch 99. Archived from the unique on 1 November 2020. Retrieved 9 April 2020.
  38. ^ a b c d “UniprotKB – Q15465 (SHH_HUMAN)”. UniProt. UniProt Consortium. Archived from the unique on 31 Might 2020. Retrieved 9 April 2020.
  39. ^ a b c d e “SHH gene”. Genetics Residence Reference. U.S. Nationwide Library of Medication. Archived from the unique on 2 April 2020. Retrieved 9 April 2020.
  40. ^ Litingtung Y, Chiang C (October 2000). “Management of Shh exercise and signaling within the neural tube”. Developmental Dynamics. 219 (2): 143–154. doi:10.1002/1097-0177(2000)9999:9999<::AID-DVDY1050>3.0.CO;2-Q. PMID 11002335. S2CID 221646338.
  41. ^ Placzek M (August 1995). “The function of the notochord and flooring plate in inductive interactions”. Present Opinion in Genetics & Improvement. 5 (4): 499–506. doi:10.1016/0959-437X(95)90055-L. PMID 7580143.
  42. ^ Teillet MA, Lapointe F, Le Douarin NM (September 1998). “The relationships between notochord and floor plate in vertebrate development revisited”. Proceedings of the Nationwide Academy of Sciences of america of America. 95 (20): 11733–11738. Bibcode:1998PNAS…9511733T. doi:10.1073/pnas.95.20.11733. PMC 21709. PMID 9751734.
  43. ^ van Straaten HW, Hekking JW, Thors F, Wiertz-Hoessels EL, Drukker J (October 1985). “Induction of an extra flooring plate within the neural tube”. Acta Morphologica Neerlando-Scandinavica. 23 (2): 91–97. PMID 3834777.
  44. ^ Patten I, Placzek M (November 2000). “The function of Sonic hedgehog in neural tube patterning”. Mobile and Molecular Life Sciences. 57 (12): 1695–1708. doi:10.1007/PL00000652. PMID 11130176. S2CID 20950575.
  45. ^ Martí E, Bumcrot DA, Takada R, McMahon AP (Might 1995). “Requirement of 19K type of Sonic hedgehog for induction of distinct ventral cell sorts in CNS explants”. Nature. 375 (6529): 322–325. Bibcode:1995Natur.375..322M. doi:10.1038/375322a0. PMID 7753196. S2CID 4362006.
  46. ^ a b c Ericson J, Morton S, Kawakami A, Roelink H, Jessell TM (November 1996). “Two vital durations of Sonic Hedgehog signaling required for the specification of motor neuron identification”. Cell. 87 (4): 661–673. doi:10.1016/S0092-8674(00)81386-0. PMID 8929535. S2CID 11578260.
  47. ^ Chiang C, Litingtung Y, Lee E, Younger KE, Corden JL, Westphal H, Beachy PA (October 1996). “Cyclopia and faulty axial patterning in mice missing Sonic hedgehog gene perform”. Nature. 383 (6599): 407–413. Bibcode:1996Natur.383..407C. doi:10.1038/383407a0. PMID 8837770. S2CID 4339131.
  48. ^ Placzek M, Tessier-Lavigne M, Yamada T, Jessell T, Dodd J (November 1990). “Mesodermal management of neural cell identification: flooring plate induction by the notochord”. Science. 250 (4983): 985–988. Bibcode:1990Sci…250..985P. doi:10.1126/science.2237443. PMID 2237443.
  49. ^ a b c Wilson L, Maden M (June 2005). “The mechanisms of dorsoventral patterning within the vertebrate neural tube”. Developmental Biology. 282 (1): 1–13. doi:10.1016/j.ydbio.2005.02.027. PMID 15936325.
  50. ^ Stone DM, Hynes M, Armanini M, Swanson TA, Gu Q, Johnson RL, et al. (November 1996). “The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog”. Nature. 384 (6605): 129–134. Bibcode:1996Natur.384..129S. doi:10.1038/384129a0. PMID 8906787. S2CID 4342540.
  51. ^ Marigo V, Tabin CJ (September 1996). “Regulation of patched by sonic hedgehog in the developing neural tube”. Proceedings of the Nationwide Academy of Sciences of america of America. 93 (18): 9346–9351. Bibcode:1996PNAS…93.9346M. doi:10.1073/pnas.93.18.9346. PMC 38430. PMID 8790332.
  52. ^ a b Ericson J, Briscoe J, Rashbass P, van Heyningen V, Jessell TM (1997). “Graded sonic hedgehog signaling and the specification of cell destiny within the ventral neural tube”. Chilly Spring Harbor Symposia on Quantitative Biology. 62: 451–466. doi:10.1101/SQB.1997.062.01.053. PMID 9598380.
  53. ^ Ericson J, Rashbass P, Schedl A, Brenner-Morton S, Kawakami A, van Heyningen V, et al. (July 1997). “Pax6 controls progenitor cell identification and neuronal destiny in response to graded Shh signaling”. Cell. 90 (1): 169–180. doi:10.1016/S0092-8674(00)80323-2. PMID 9230312. S2CID 17054686.
  54. ^ Lum L, Beachy PA (June 2004). “The Hedgehog response community: sensors, switches, and routers”. Science. 304 (5678): 1755–1759. Bibcode:2004Sci…304.1755L. CiteSeerX 10.1.1.476.3902. doi:10.1126/science.1098020. PMID 15205520. S2CID 13949436.
  55. ^ a b Ruiz i Altaba A (June 1998). “Combinatorial Gli gene perform in flooring plate and neuronal inductions by Sonic hedgehog”. Improvement. 125 (12): 2203–2212. doi:10.1242/dev.125.12.2203. PMID 9584120.
  56. ^ Park HL, Bai C, Platt KA, Matise MP, Beeghly A, Hui CC, et al. (April 2000). “Mouse Gli1 mutants are viable however have defects in SHH signaling together with a Gli2 mutation”. Improvement. 127 (8): 1593–1605. doi:10.1242/dev.127.8.1593. PMID 10725236.
  57. ^ Matise MP, Epstein DJ, Park HL, Platt KA, Joyner AL (August 1998). “Gli2 is required for induction of flooring plate and adjoining cells, however not most ventral neurons within the mouse central nervous system”. Improvement. 125 (15): 2759–2770. doi:10.1242/dev.125.15.2759. PMID 9655799.
  58. ^ a b c Litingtung Y, Chiang C (October 2000). “Specification of ventral neuron sorts is mediated by an antagonistic interplay between Shh and Gli3”. Nature Neuroscience. 3 (10): 979–985. doi:10.1038/79916. PMID 11017169. S2CID 10102370.
  59. ^ Sasaki H, Nishizaki Y, Hui C, Nakafuku M, Kondoh H (September 1999). “Regulation of Gli2 and Gli3 actions by an amino-terminal repression area: implication of Gli2 and Gli3 as main mediators of Shh signaling”. Improvement. 126 (17): 3915–3924. doi:10.1242/dev.126.17.3915. PMID 10433919.
  60. ^ Persson M, Stamataki D, te Welscher P, Andersson E, Böse J, Rüther U, et al. (November 2002). “Dorsal-ventral patterning of the spinal cord requires Gli3 transcriptional repressor activity”. Genes & Improvement. 16 (22): 2865–2878. doi:10.1101/gad.243402. PMC 187477. PMID 12435629.
  61. ^ Chuang PT, McMahon AP (February 1999). “Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein”. Nature. 397 (6720): 617–621. Bibcode:1999Natur.397..617C. doi:10.1038/17611. PMID 10050855. S2CID 204991314.
  62. ^ Pons S, Martí E (January 2000). “Sonic hedgehog synergizes with the extracellular matrix protein vitronectin to induce spinal motor neuron differentiation”. Improvement. 127 (2): 333–342. doi:10.1242/dev.127.2.333. PMID 10603350.
  63. ^ Briscoe J, Pierani A, Jessell TM, Ericson J (Might 2000). “A homeodomain protein code specifies progenitor cell identification and neuronal destiny within the ventral neural tube”. Cell. 101 (4): 435–445. doi:10.1016/S0092-8674(00)80853-3. PMID 10830170. S2CID 17295764.
  64. ^ Liem KF, Jessell TM, Briscoe J (November 2000). “Regulation of the neural patterning exercise of sonic hedgehog by secreted BMP inhibitors expressed by notochord and somites”. Improvement. 127 (22): 4855–4866. doi:10.1242/dev.127.22.4855. PMID 11044400.
  65. ^ McMahon JA, Takada S, Zimmerman LB, Fan CM, Harland RM, McMahon AP (Might 1998). “Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite”. Genes & Improvement. 12 (10): 1438–1452. doi:10.1101/gad.12.10.1438. PMC 316831. PMID 9585504.
  66. ^ a b c d e f g h i j Ribes V, Briscoe J (August 2009). “Establishing and interpreting graded Sonic Hedgehog signaling during vertebrate neural tube patterning: the role of negative feedback”. Chilly Spring Harbor Views in Biology. 1 (2): a002014. doi:10.1101/cshperspect.a002014. PMC 2742090. PMID 20066087.
  67. ^ Muroyama Y, Fujihara M, Ikeya M, Kondoh H, Takada S (March 2002). “Wnt signaling plays an essential role in neuronal specification of the dorsal spinal cord”. Genes & Improvement. 16 (5): 548–553. doi:10.1101/gad.937102. PMC 155351. PMID 11877374.
  68. ^ 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”. Improvement. 135 (6): 1097–1106. doi:10.1242/dev.013086. PMID 18272593. S2CID 17431502.
  69. ^ Lovrics A, Gao Y, Juhász B, Bock I, Byrne HM, Dinnyés A, Kovács KA (November 2014). “Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord”. PLOS ONE. 9 (11): e111430. Bibcode:2014PLoSO…9k1430L. doi:10.1371/journal.pone.0111430. PMC 4232242. PMID 25398016.
  70. ^ Richbourg HA, Hu DP, Xu Y, Barczak AJ, Marcucio RS (September 2020). “miR-199 family contributes to regulation of sonic hedgehog expression during craniofacial development”. Developmental Dynamics. 249 (9): 1062–1076. doi:10.1002/dvdy.191. PMC 7484444. PMID 32391617.
  71. ^ Nanci A (2012). Ten Cate’s Oral Histology: Improvement, Construction, and Operate (eighth ed.). St. Louis, Mo.: Elsevier. ISBN 978-0-323-07846-7.
  72. ^ Thesleff I (Might 2003). “Epithelial-mesenchymal signalling regulating tooth morphogenesis”. Journal of Cell Science. 116 (Pt 9): 1647–1648. doi:10.1242/jcs.00410. PMID 12665545. S2CID 45648812.
  73. ^ Hardcastle Z, Mo R, Hui CC, Sharpe PT (August 1998). “The Shh signalling pathway in tooth growth: defects in Gli2 and Gli3 mutants”. Improvement. 125 (15): 2803–2811. doi:10.1242/dev.125.15.2803. PMID 9655803.
  74. ^ Wolpert L (2015). Rules of Improvement (fifth ed.). Oxford College Press. p. 500. ISBN 978-0-19-967814-3.
  75. ^ Bellusci S, Furuta Y, Rush MG, Henderson R, Winnier G, Hogan BL (January 1997). “Involvement of Sonic hedgehog (Shh) in mouse embryonic lung development and morphogenesis”. Improvement. 124 (1): 53–63. doi:10.1242/dev.124.1.53. PMID 9006067.
  76. ^ a b c d e Pepicelli CV, Lewis PM, McMahon AP (September 1998). “Sonic hedgehog regulates branching morphogenesis within the mammalian lung”. Present Biology. 8 (19): 1083–1086. doi:10.1016/S0960-9822(98)70446-4. PMID 9768363. S2CID 12711144.
  77. ^ White AC, Xu J, Yin Y, Smith C, Schmid G, Ornitz DM (April 2006). “FGF9 and SHH signaling coordinate lung growth and development through regulation of distinct mesenchymal domains”. Improvement. 133 (8): 1507–1517. doi:10.1242/dev.02313. PMID 16540513. S2CID 23839558.
  78. ^ Miura T (2008). Modeling lung branching morphogenesis. Present Matters in Developmental Biology. Vol. 81. pp. 291–310. doi:10.1016/S0070-2153(07)81010-6. ISBN 9780123742537. PMID 18023732.
  79. ^ a b c Kugler MC, Joyner AL, Loomis CA, Munger JS (January 2015). “Sonic hedgehog signaling in the lung. From development to disease”. American Journal of Respiratory Cell and Molecular Biology. 52 (1): 1–13. doi:10.1165/rcmb.2014-0132TR. PMC 4370254. PMID 25068457.
  80. ^ Cardoso WV, Lü J (Might 2006). “Regulation of early lung morphogenesis: questions, facts and controversies”. Improvement. 133 (9): 1611–1624. doi:10.1242/dev.02310. PMID 16613830. S2CID 18195361.
  81. ^ Lu N, Chen Y, Wang Z, Chen G, Lin Q, Chen ZY, Li H (January 2013). “Sonic hedgehog initiates cochlear hair cell regeneration through downregulation of retinoblastoma protein”. Biochemical and Biophysical Analysis Communications. 430 (2): 700–705. doi:10.1016/j.bbrc.2012.11.088. PMC 3579567. PMID 23211596.
  82. ^ Zhang B, Tsai PC, Gonzalez-Celeiro M, Chung O, Boumard B, Perdigoto CN, et al. (October 2016). “Hair follicles’ transit-amplifying cells govern concurrent dermal adipocyte production through Sonic Hedgehog”. Genes & Improvement. 30 (20): 2325–2338. doi:10.1101/gad.285429.116. PMC 5110998. PMID 27807033.
  83. ^ Bumcrot DA, Takada R, McMahon AP (April 1995). “Proteolytic processing yields two secreted forms of sonic hedgehog”. Molecular and Mobile Biology. 15 (4): 2294–2303. doi:10.1128/MCB.15.4.2294. PMC 230457. PMID 7891723.
  84. ^ Ingham PW, Nakano Y, Seger C (June 2011). “Mechanisms and capabilities of Hedgehog signalling throughout the metazoa”. Nature Opinions. Genetics. 12 (6): 393–406. doi:10.1038/nrg2984. PMID 21502959. S2CID 33769324.
  85. ^ Porter JA, Younger KE, Beachy PA (October 1996). “Ldl cholesterol modification of hedgehog signaling proteins in animal growth”. Science. 274 (5285): 255–259. Bibcode:1996Sci…274..255P. doi:10.1126/science.274.5285.255. PMID 8824192. S2CID 11125394.
  86. ^ Pepinsky RB, Zeng C, Wen D, Rayhorn P, Baker DP, Williams KP, et al. (Might 1998). “Identification of a palmitic acid-modified form of human Sonic hedgehog”. The Journal of Organic Chemistry. 273 (22): 14037–14045. doi:10.1074/jbc.273.22.14037. PMID 9593755. S2CID 22783982.
  87. ^ Stanton BZ, Peng LF, Maloof N, Nakai Okay, Wang X, Duffner JL, et al. (March 2009). “A small molecule that binds Hedgehog and blocks its signaling in human cells”. Nature Chemical Biology. 5 (3): 154–156. doi:10.1038/nchembio.142. PMC 2770933. PMID 19151731.
  88. ^ Maclean Okay (January 2006). “Humour of gene names lost in translation to patients”. Nature. 439 (7074): 266. Bibcode:2006Natur.439..266M. doi:10.1038/439266d. PMID 16421543. S2CID 19861153.
  89. ^ Cohen MM (July 2006). “Issues within the naming of genes”. American Journal of Medical Genetics. Half A. 140 (13): 1483–1484. doi:10.1002/ajmg.a.31264. PMID 16718675. S2CID 221388561.
  90. ^ White M (September 26, 2014). “Sonic Hedgehog, DICER, and the Problem With Naming Genes”. psmag.com. Pacific Normal. Archived from the unique on November 12, 2020. Retrieved December 24, 2020.
  91. ^ Hopkin M (November 6, 2006). “Troublesome gene names get the boot”. Nature: news061106–2. doi:10.1038/news061106-2. S2CID 86514270. Archived from the unique on December 31, 2020. Retrieved December 24, 2020.

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