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 region • extracellular space • extracellular space • membrane fraction • 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 • vasculature development • heart looping • positive regulation of neuroblast proliferation • osteoblast development • lymphoid progenitor cell differentiation • determination of left/right asymmetry in lateral mesoderm • endocytosis • signal transduction • smoothened signaling pathway • 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 • cell death • positive regulation of cell proliferation • positive regulation of cell proliferation • embryo development • embryonic pattern specification • anterior/posterior pattern specification • dorsal/ventral pattern formation • response to organic nitrogen • negative regulation of gene expression • oligodendrocyte development • striated muscle tissue development • positive regulation of skeletal muscle cell proliferation • myotube differentiation • intein-mediated protein splicing • spinal cord dorsal/ventral patterning • ventral spinal cord interneuron specification • dorsal/ventral neural tube patterning • smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation • positive regulation of cerebellar granule cell precursor 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 • positive regulation of activin receptor signaling pathway • 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 organ development • developmental growth • 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 • limb development • 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 • 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
Species	Human	Mouse
Entrez	6469	20423
Ensembl	ENSG00000164690	ENSMUSG00000002633
UniProt	Q15465	Q62226
RefSeq (mRNA)	NM_000193.2	NM_009170.3
RefSeq (protein)	NP_000184.1	NP_033196.1
Location (UCSC)	Chr 7: 155.59 – 155.6 Mb	Chr 5: 28.78 – 28.79 Mb
PubMed search	[1]	[2]
This box: view talk edit

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[link]

The hedgehog gene (hh) was first identified in the classic Heidelberg screens of Eric Wieschaus and Christiane Nusslein-Volhard, as published in 1980. These screens, which led to their winning the Nobel Prize in 1995 along with developmental geneticist Edward B. Lewis, identified genes that control the segmentation pattern of Drosophila melanogaster (fruit fly) embryos. The hh loss of function mutant phenotype causes the embryos to be covered with denticles (small pointy projections), 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[link]

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[link]

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[link]

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[link]

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[link]

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.^[45]

Criticism of the name[link]

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."^[46][47]

See also[link]

• Zbtb7, a gene which was originally named "Pokémon"
• Pikachurin, a retinal protein named after Pikachu

References[link]

Further reading[link]

External links[link]

• 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

v t e PDB gallery 1vhh: A POTENTIAL CATALYTIC SITE WITHIN THE AMINO-TERMINAL SIGNALLING DOMAIN OF SONIC HEDGEHOG

Daddy Yankee
Background information
Birth name	Ramón Ayala
Also known as	Winchester 30-30 El Cangri El Jefe The Big Boss DY El Máximo Lider
Born	(1977-02-03) February 3, 1977 (age 35)
Origin	San Juan, Puerto Rico
Genres	Reggaeton, Latin rap, hip-hop
Years active	1992–present
Labels	El Cartel, Interscope, Sony Music Latin
Website	daddyyankee.com

Ramón Luis Ayala Rodríguez (born February 3, 1977), known artistically as Daddy Yankee, is a Latin Grammy Award-winning Puerto Rican reggaeton recording artist. Ayala was born in Río Piedras, the largest district of San Juan, where he became interested in music at a young age. In his youth he was interested in baseball, and aspired to become a Major League Baseball player. He was unable to continue this sport when he received an injury to one of his legs, leaving him unable to walk correctly. He then became involved in the underground rap movement that was in its early stages in Puerto Rico, later to be called reggaeton. After receiving lessons from several artists within the genre, he developed an independent career, first recording in a production titled Playero 37. After this he began to produce independent albums. His first solo album was No Mercy. He subsequently formed a duo with Nicky Jam, and then continued his solo career with the releases of El Cartel and El Cartel II. This led him be one of many pioneers of the reggaeton genre earning him the nickname "El Cangri".

In 2002 El Cangri.com became Ayala's first album with international success, receiving coverage in the markets of New York and Miami. Barrio Fino was released in 2004, and the album received numerous awards, including Lo Nuestro Awards and a Latin Billboard, as well as receiving nominations for the Latin Grammy and MTV Video Music Awards. Barrio Fino performed well in the sales charts of the United States, Latin America, Europe, and Japan. On June 5, 2007, El Cartel Records released El Cartel: The Big Boss, which was ranked as the top-selling album in Latin music genres in 2007. He promoted the album with an international tour which began in the United States and continued through Latin America, breaking attendance records in Ecuador and Bolivia.

His performances have appeared on more than 70 albums, including compilations such as Mas Flow 2 and Blin Blin Vol. 1. Outside of his work as a musician, Ayala has also worked as an actor and producer. Throughout his career, he has been generally reluctant to discuss his personal life, but has publicly expressed the importance of his wife and children to him.

Following the incident, he became interested in the underground movement, which at the time was in an early organizational stage.^[1] He also took more interest in the events that took place in the neighborhood in which he was raised, a public housing project named Villa Kennedy.^[2] Early in his career he attempted to imitate the style of Vico C. He went on to emulate other artists in the genre, including DJ Playero, DJ Nelson, and DJ Goldy, taking elements from their styles in order to develop an original style.^[1] In doing so, he eventually abandoned the traditional model of rap and became one of the first artists to perform reggaeton.^[1] Ayala first recorded with DJ Playero as a featured artist in a production titled Playero 37, which was released in 1992.^[2]

Musical career[link]

Independent productions[link]

His first album, titled No Mercy, was produced in 1995 when Ayala was eighteen years old.^[2] The production did not sell well, and he continued his work within the genre for the rest of the decade, eventually forming a duo with Nicky Jam. One of the duo's songs, "Posición", was included in the soundtrack of One Tough Cop, a movie directed by Bruno Barreto, that was released in 1998. Beginning in 2000, Ayala began concentrating more on his solo career, releasing albums produced outside studios. The first production he released was titled El Cartel, featuring elements of the mixtape style.^[2] In 2001 El Cartel II was released, a direct sequel to the previous production, and influenced by similar genres.

In 2005 El Cangri.com was released, and became the first album in Ayala's career to sell well outside Puerto Rico, mostly in the United States.^[2] The album was produced by VI Music, an independent recording studio in Puerto Rico, and was not supported by a major label.^[2] The most successful single from the album was "Latigazo", which received significant play on radio stations in New York and Miami.^[2] The album reached #43 on Billboard's Top Latin Albums chart.^[2] Following the release of this disc, Ayala performed at the Roberto Clemente Coliseum before 12,000 fans.^[3] The following year VI Music produced Los Homerun-es.^[2] The album became the leader in sales in Puerto Rico during a year in which several other reggaeton artists released significant productions, including Luny Tune's Mas Flow, Don Omar's The Last Don, and Tego Calderón's El Abayarde.^[2] The album's success helped Ayala receive the publicity required for a crossover to the United States market, and marked the last album he released with VI music before signing a contract with Universal

2004–2005[link]

Ayala's next album, Barrio Fino, was produced by Luny Tunes and released in July 2004 by El Cartel Records and VI Music. It was the most highly anticipated album in the reggaeton community.^[4] Ayala had enjoyed Salsa music since he was young, and this led him to include music of genres besides reggaeton in the album.^[4] The most prominent of these cross-genre singles was "Melao", in which he performed with Andy Montañez.^[4] The album was described as his most complete, and with it he intended to introduce combinations of reggaeton and other genres to the English-speaking market.^[4] Barrio Fino was followed up by an international tour with performances in numerous countries including the Dominican Republic, Ecuador, Mexico, Panama, Peru, Honduras, Spain, Colombia, Argentina, Venezuela, and the United States.^[4] The album has sold over 500,000 copies in the United States alone and has sold well throughout Latin America and worldwide.^[5]

In 2005 Ayala won several international awards, making him one of the most recognized reggaeton artists within the music industry.^[6] The first award of the year was Lo Nuestro Awards within the "Latin music" category, which he received for Barrio Fino.^[6] In this event he performed "Gasolina" in a performance that was described as "innovative".^[6] Barrio Fino also won the "Reggaeton Album of the Year" award in the Latin Billboard that took place on April 28, 2005,^[6] where he performed a mix of three of his songs in a duo with P. Diddy. The album was promoted throughout Latin America, the United States, and Europe, reaching certified gold in Japan. Due to the album's success, Ayala received promotional contracts with radio stations and soda companies, including Pepsi.^[7] His single "Gasolina" received the majority of votes cast for the second edition of Premios Juventud, in which it received eight nominations and won seven awards.^[6] Ayala also made a live presentation during the award ceremony. "Gasolina" received nominations in the Latin Grammy and MTV Video Music Awards.^[6]

The successful single, "Gasolina", was covered by artists from different music genres. This led to a controversy when Los Lagos, a Mexican banda group, did a cover with the original beat but changed the song's lyrics.^[8] The group's label had solicited the copyright permission to perform the single and translate it to a different music style, but did not receive consent to change the lyrics; legal action followed.^[8] Speaking for the artist, Ayala's lawyer stated that having his songs covered was an "honor, but it must be done the right way."^[8]

2006–present[link]

On April 30, 2006, Ayala was named one of the 100 most influential people by Time magazine, which cited the 2 million copies of Barrio Fino sold, Ayala's $20 million contract with Interscope Records, and his Pepsi endorsement.^[9] During this period, Ayala and William Omar Landrón (more commonly known by his artistic name Don Omar) were involved in a rivalry within the genre, dubbed "tiraera". The rivalry received significant press coverage despite being denied early on by both artists. It originated with a lyrical conflict between the artists begun by Ayala's comments in a remix single, where he criticized Landron's common usage of the nickname "King of Kings".^[10] Don Omar responded to this in a song titled "Ahora Son Mejor", part of his album Los Rompediscotecas.^[10]

El Cartel: The Big Boss was released by Interscope on June 5, 2007. Ayala stated that the album marked a return to his hip-hop roots as opposed to being considered a strictly reggaeton album.^[11] The album was produced in 2006, and included the participation of will.i.am, Scott Storch, Tainy Tunes, Neli, and personnel from Ayala's label. Singles were produced with Héctor Delgado, Fergie, Nicole Scherzinger and Akon.^[11] The first single from the album was titled "Impacto", and was released prior to the completion of the album. The album was promoted by a tour throughout the United States, which continued throughout Latin America.^[11] He performed in Mexico, first in Monterrey, where 10,000 attended the concert, and later at San Luis Potosí coliseum, where the concert sold out, leaving hundreds of fans outside the building.^[12] Ayala performed in Chile as well, and established a record for attendance in Ecuador.^[13] He also performed in Bolivia, setting another record when 50,000 fans attended his Santa Cruz de la Sierra concert.^[13] This show was later described as "the best show with the biggest attendance in history" and as "somehappy that his album had sold more than those of Juan Luis Guerra and Juanes, and that this was an "official proof that reggaeton's principal exponent defeated the rest of the genres".^[14] Ayala made a guest appearance in an album titled "Caribbean he loved the color reed|Inner Circle]], Bounty Killer, Elephant Man and Wayne Wonder.^[15] In July 2008, Ayala announced that as part of his work, he would produce a cover version of Thalía's song, Ten Paciencia.^[16] Prior to the album's release, Ayala scheduled several activities, including an in-store contract signing.^[17] On February 27, 2009, he performed at the Viña del Mar International Song Festival in Chile.^[18] In this event, the artists receive awards based on the public's reaction. After performing "Rompe", "Llamado de emergencia", "Tú me dejaste caer", "Gasolina", "Limpia parabrisas" and "Lo que pasó, pasó" over the course of two hours, Ayala received the "Silver Torch", "Gold Torch" and "Silver Seagull" recognitions.^[18] On April 24, 2009, he received the Spirit of Hope Award as part of the Latin Billboard Music Awards ceremony.^[19] The recognition is given to the artists that participate in community or social efforts throughout the year. The single "Grito Mundial" was released on October 8, 2009,^[20] in order to promote his ninth album, Mundial. Despite releasing "El Ritmo No Perdona (Prende)" more than a month before, that single was not considered the first official promotional single.

Film and other career projects[link]

Ayala has negotiated promotional deals with several companies outside of the music industry, releasing merchandise under his name. In 2005, he became the first Latin artist to sign a deal with Reebok, in order to produce accessories,^[21] including the licensed clothing line "DY", which was released in 2006.^[22] He also teamed up with the company to have his own shoes and sporting goods made, which were first distributed on May 23, 2006.^[11] Reebok continued the partnership with the introduction of the Travel Trainer collection in July 2007. In August 2007, Pepsi began an advertising campaign titled "Puertas", in which Ayala is depicted returning to his youth by opening a series of doors.^[23]

In 2008, Ayala participated in a campaign to promote voting in the 2008 general elections in Puerto Rico. This initiative included a concert titled "Vota o quédate callao".^[24] On August 25, 2008, Ayala endorsed John McCain's candidacy for President of the United States, stating that McCain "has been a fighter for the Hispanic community".^[25] As part of this campaign, Ayala moderated a debate titled “Vota o quédate callao: los candidatos responden a los jóvenes”, which was aired on October 9, 2008.^[26]

Ayala has worked in the film industry as both an actor and producer. His acting debut was the lead role of Vampiros, a film directed by Eduardo Ortiz and filmed in Puerto Rico.^[27] The film premiered at the Festival of Latin American Cinema in New York, where it received a positive reaction. This led Image Entertainment to produce a DVD, internationally released in March 2005.^[27] Ayala played the main role "Edgar" in Talento de Barrio, which was filmed in Puerto Rico and directed by José Iván Santiago. Ayala produced the film, which is based on his experience of growing up in a poor city neighborhood.^[28] While the film is not directly a biography, Ayala has stated that it mirrors his early life.^[28] Talento de Barrio's debut was scheduled for July 23, 2008, in New York's Latino Film Festival.^[29] After the premier, Ayala expressed satisfaction, saying that he had been invited to audition for other producers.^[30] On release, Talento de Barrio broke the record held by Maldeamores for the most tickets to a Puerto Rican movie sold in a single day in Caribbean Cinemas.^[31]

Ayala has been involved in the administration of three organizations, the first being El Cartel Records which he co-owns with Andres Hernandez. He also created the Fundación Corazón Guerrero, a charitable organization in Puerto Rico which works with young incarcerated people.^[32] On April 26, 2008, he was presented with a "Latino of the Year Award" by the student organization Presencia Latina of Harvard College, receiving it for his work with Puerto Rican youth and creating Corazón Guerrero.^[33] On February 6, 2008, Ayala announced in a Baloncesto Superior Nacional press conference that he had bought part of the Criollos de Caguas' ownership.^[34]

Personal life[link]

Ayala has kept most of his personal life private, rarely speaking about it in interviews.^[35] He has said that he avoids doing so because such details are the only aspect of his life that are not public and that they are like a "little treasure".^[35] He made an exception in 2006 when he spoke about his relationship with his wife and children in an interview with María Celeste Arrarás in Al Rojo Vivo.^[35] He stated that his marriage is strong because he and his wife are "friends above anything", adding that he has tried to ignore other temptations because "weakness is the reason for the downfall of several artists."^[35] He also described his "very close" communication with his children, in which he tries to offer advice against drugs and negative influences.^[35] His first daughter was born when he was seventeen years old,^[35] which he has described as confusing at first, adding that raising a daughter at that age was a hard experience.^[36]

Studio albums[link]

• 1995: No Mercy
• 2002: El Cangri.com
• 2004: Barrio Fino
• 2007: El Cartel: The Big Boss
• 2010: Daddy Yankee Mundial
• 2012: Prestige

Filmography[link]

Film

Television

See also[link]

	Biography portal
	Puerto Rico portal
	Music portal

• Latin American music
• List of Caribbean music genres
• List of Puerto Ricans
• List of Puerto Rican songwriters
• Urban contemporary

References[link]

External links[link]

• Official site
• Daddy Yankee at the Internet Movie Database