Protein-Trap Insertional Mutagenesis Uncovers New Genes Involved in Zebrafish Skin Development, Including a Neuregulin 2a-Based ErbB Signaling Pathway Required during Median Fin Fold Morphogenesis
Skin disorders are widespread, but available treatments are limited. A more comprehensive understanding of skin development mechanisms will drive identification of new treatment targets and modalities. Here we report the Zebrafish Integument Project (ZIP), an expression-driven platform for identifyi...
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| Veröffentlicht in: | PloS one 2015-06, Vol.10 (6), p.e0130688 |
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| creator | Westcot, Stephanie E Hatzold, Julia Urban, Mark D Richetti, Stefânia K Skuster, Kimberly J Harm, Rhianna M Lopez Cervera, Roberto Umemoto, Noriko McNulty, Melissa S Clark, Karl J Hammerschmidt, Matthias Ekker, Stephen C |
| description | Skin disorders are widespread, but available treatments are limited. A more comprehensive understanding of skin development mechanisms will drive identification of new treatment targets and modalities. Here we report the Zebrafish Integument Project (ZIP), an expression-driven platform for identifying new skin genes and phenotypes in the vertebrate model Danio rerio (zebrafish). In vivo selection for skin-specific expression of gene-break transposon (GBT) mutant lines identified eleven new, revertible GBT alleles of genes involved in skin development. Eight genes--fras1, grip1, hmcn1, msxc, col4a4, ahnak, capn12, and nrg2a--had been described in an integumentary context to varying degrees, while arhgef25b, fkbp10b, and megf6a emerged as novel skin genes. Embryos homozygous for a GBT insertion within neuregulin 2a (nrg2a) revealed a novel requirement for a Neuregulin 2a (Nrg2a)-ErbB2/3-AKT signaling pathway governing the apicobasal organization of a subset of epidermal cells during median fin fold (MFF) morphogenesis. In nrg2a mutant larvae, the basal keratinocytes within the apical MFF, known as ridge cells, displayed reduced pAKT levels as well as reduced apical domains and exaggerated basolateral domains. Those defects compromised proper ridge cell elongation into a flattened epithelial morphology, resulting in thickened MFF edges. Pharmacological inhibition verified that Nrg2a signals through the ErbB receptor tyrosine kinase network. Moreover, knockdown of the epithelial polarity regulator and tumor suppressor lgl2 ameliorated the nrg2a mutant phenotype. Identifying Lgl2 as an antagonist of Nrg2a-ErbB signaling revealed a significantly earlier role for Lgl2 during epidermal morphogenesis than has been described to date. Furthermore, our findings demonstrated that successive, coordinated ridge cell shape changes drive apical MFF development, making MFF ridge cells a valuable model for investigating how the coordinated regulation of cell polarity and cell shape changes serves as a crucial mechanism of epithelial morphogenesis. |
| doi_str_mv | 10.1371/journal.pone.0130688 |
| format | Article |
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A more comprehensive understanding of skin development mechanisms will drive identification of new treatment targets and modalities. Here we report the Zebrafish Integument Project (ZIP), an expression-driven platform for identifying new skin genes and phenotypes in the vertebrate model Danio rerio (zebrafish). In vivo selection for skin-specific expression of gene-break transposon (GBT) mutant lines identified eleven new, revertible GBT alleles of genes involved in skin development. Eight genes--fras1, grip1, hmcn1, msxc, col4a4, ahnak, capn12, and nrg2a--had been described in an integumentary context to varying degrees, while arhgef25b, fkbp10b, and megf6a emerged as novel skin genes. Embryos homozygous for a GBT insertion within neuregulin 2a (nrg2a) revealed a novel requirement for a Neuregulin 2a (Nrg2a)-ErbB2/3-AKT signaling pathway governing the apicobasal organization of a subset of epidermal cells during median fin fold (MFF) morphogenesis. In nrg2a mutant larvae, the basal keratinocytes within the apical MFF, known as ridge cells, displayed reduced pAKT levels as well as reduced apical domains and exaggerated basolateral domains. Those defects compromised proper ridge cell elongation into a flattened epithelial morphology, resulting in thickened MFF edges. Pharmacological inhibition verified that Nrg2a signals through the ErbB receptor tyrosine kinase network. Moreover, knockdown of the epithelial polarity regulator and tumor suppressor lgl2 ameliorated the nrg2a mutant phenotype. Identifying Lgl2 as an antagonist of Nrg2a-ErbB signaling revealed a significantly earlier role for Lgl2 during epidermal morphogenesis than has been described to date. Furthermore, our findings demonstrated that successive, coordinated ridge cell shape changes drive apical MFF development, making MFF ridge cells a valuable model for investigating how the coordinated regulation of cell polarity and cell shape changes serves as a crucial mechanism of epithelial morphogenesis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0130688</identifier><identifier>PMID: 26110643</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>AKT protein ; Alleles ; Animal Fins - embryology ; Animal Fins - metabolism ; Animal genetic engineering ; Animals ; Biochemistry ; Breast cancer ; Cell size ; Cytology ; Danio rerio ; Developmental biology ; Disease ; Elongation ; Embryos ; ErbB protein ; ErbB-2 protein ; Gene expression ; Gene Expression Regulation, Developmental ; Genes ; Genetic aspects ; Genetics ; Genomics ; GRIP1 protein ; Insertional mutagenesis ; Integument ; Keratinocytes ; Kinases ; Larvae ; Localization ; Mammals ; Medical research ; Molecular biology ; Morphogenesis ; Mutagenesis ; Mutagenesis, Insertional ; Neuregulin ; Neuregulins - genetics ; Neuregulins - metabolism ; Oncogene Proteins v-erbB - genetics ; Oncogene Proteins v-erbB - metabolism ; Organogenesis - genetics ; Pharmacology ; Phenotypes ; Polarity ; Protein-tyrosine kinase receptors ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; Signal transduction ; Signal Transduction - genetics ; Signaling ; Skin ; Skin - embryology ; Skin - metabolism ; Skin diseases ; Target recognition ; Tumor suppressor genes ; Tyrosine ; Zebrafish ; Zebrafish - embryology ; Zebrafish - genetics ; Zebrafish - metabolism ; Zebrafish Proteins - genetics ; Zebrafish Proteins - metabolism</subject><ispartof>PloS one, 2015-06, Vol.10 (6), p.e0130688</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Westcot et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Westcot et al 2015 Westcot et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-9e2489a4e6ae57fdd12cf3ceb371f34e7e0a9ad29e47d4763632e0cb2735a283</citedby><cites>FETCH-LOGICAL-c758t-9e2489a4e6ae57fdd12cf3ceb371f34e7e0a9ad29e47d4763632e0cb2735a283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482254/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482254/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26110643$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Westcot, Stephanie E</creatorcontrib><creatorcontrib>Hatzold, Julia</creatorcontrib><creatorcontrib>Urban, Mark D</creatorcontrib><creatorcontrib>Richetti, Stefânia K</creatorcontrib><creatorcontrib>Skuster, Kimberly J</creatorcontrib><creatorcontrib>Harm, Rhianna M</creatorcontrib><creatorcontrib>Lopez Cervera, Roberto</creatorcontrib><creatorcontrib>Umemoto, Noriko</creatorcontrib><creatorcontrib>McNulty, Melissa S</creatorcontrib><creatorcontrib>Clark, Karl J</creatorcontrib><creatorcontrib>Hammerschmidt, Matthias</creatorcontrib><creatorcontrib>Ekker, Stephen C</creatorcontrib><title>Protein-Trap Insertional Mutagenesis Uncovers New Genes Involved in Zebrafish Skin Development, Including a Neuregulin 2a-Based ErbB Signaling Pathway Required during Median Fin Fold Morphogenesis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Skin disorders are widespread, but available treatments are limited. A more comprehensive understanding of skin development mechanisms will drive identification of new treatment targets and modalities. Here we report the Zebrafish Integument Project (ZIP), an expression-driven platform for identifying new skin genes and phenotypes in the vertebrate model Danio rerio (zebrafish). In vivo selection for skin-specific expression of gene-break transposon (GBT) mutant lines identified eleven new, revertible GBT alleles of genes involved in skin development. Eight genes--fras1, grip1, hmcn1, msxc, col4a4, ahnak, capn12, and nrg2a--had been described in an integumentary context to varying degrees, while arhgef25b, fkbp10b, and megf6a emerged as novel skin genes. Embryos homozygous for a GBT insertion within neuregulin 2a (nrg2a) revealed a novel requirement for a Neuregulin 2a (Nrg2a)-ErbB2/3-AKT signaling pathway governing the apicobasal organization of a subset of epidermal cells during median fin fold (MFF) morphogenesis. In nrg2a mutant larvae, the basal keratinocytes within the apical MFF, known as ridge cells, displayed reduced pAKT levels as well as reduced apical domains and exaggerated basolateral domains. Those defects compromised proper ridge cell elongation into a flattened epithelial morphology, resulting in thickened MFF edges. Pharmacological inhibition verified that Nrg2a signals through the ErbB receptor tyrosine kinase network. Moreover, knockdown of the epithelial polarity regulator and tumor suppressor lgl2 ameliorated the nrg2a mutant phenotype. Identifying Lgl2 as an antagonist of Nrg2a-ErbB signaling revealed a significantly earlier role for Lgl2 during epidermal morphogenesis than has been described to date. Furthermore, our findings demonstrated that successive, coordinated ridge cell shape changes drive apical MFF development, making MFF ridge cells a valuable model for investigating how the coordinated regulation of cell polarity and cell shape changes serves as a crucial mechanism of epithelial morphogenesis.</description><subject>AKT protein</subject><subject>Alleles</subject><subject>Animal Fins - embryology</subject><subject>Animal Fins - metabolism</subject><subject>Animal genetic engineering</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Breast cancer</subject><subject>Cell size</subject><subject>Cytology</subject><subject>Danio rerio</subject><subject>Developmental biology</subject><subject>Disease</subject><subject>Elongation</subject><subject>Embryos</subject><subject>ErbB protein</subject><subject>ErbB-2 protein</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetics</subject><subject>Genomics</subject><subject>GRIP1 protein</subject><subject>Insertional mutagenesis</subject><subject>Integument</subject><subject>Keratinocytes</subject><subject>Kinases</subject><subject>Larvae</subject><subject>Localization</subject><subject>Mammals</subject><subject>Medical research</subject><subject>Molecular biology</subject><subject>Morphogenesis</subject><subject>Mutagenesis</subject><subject>Mutagenesis, Insertional</subject><subject>Neuregulin</subject><subject>Neuregulins - genetics</subject><subject>Neuregulins - metabolism</subject><subject>Oncogene Proteins v-erbB - genetics</subject><subject>Oncogene Proteins v-erbB - metabolism</subject><subject>Organogenesis - genetics</subject><subject>Pharmacology</subject><subject>Phenotypes</subject><subject>Polarity</subject><subject>Protein-tyrosine kinase receptors</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Signal transduction</subject><subject>Signal Transduction - genetics</subject><subject>Signaling</subject><subject>Skin</subject><subject>Skin - embryology</subject><subject>Skin - metabolism</subject><subject>Skin diseases</subject><subject>Target recognition</subject><subject>Tumor suppressor genes</subject><subject>Tyrosine</subject><subject>Zebrafish</subject><subject>Zebrafish - embryology</subject><subject>Zebrafish - genetics</subject><subject>Zebrafish - metabolism</subject><subject>Zebrafish Proteins - genetics</subject><subject>Zebrafish Proteins - 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embryology</topic><topic>Animal Fins - metabolism</topic><topic>Animal genetic engineering</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Breast cancer</topic><topic>Cell size</topic><topic>Cytology</topic><topic>Danio rerio</topic><topic>Developmental biology</topic><topic>Disease</topic><topic>Elongation</topic><topic>Embryos</topic><topic>ErbB protein</topic><topic>ErbB-2 protein</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetics</topic><topic>Genomics</topic><topic>GRIP1 protein</topic><topic>Insertional mutagenesis</topic><topic>Integument</topic><topic>Keratinocytes</topic><topic>Kinases</topic><topic>Larvae</topic><topic>Localization</topic><topic>Mammals</topic><topic>Medical research</topic><topic>Molecular biology</topic><topic>Morphogenesis</topic><topic>Mutagenesis</topic><topic>Mutagenesis, Insertional</topic><topic>Neuregulin</topic><topic>Neuregulins - genetics</topic><topic>Neuregulins - metabolism</topic><topic>Oncogene Proteins v-erbB - genetics</topic><topic>Oncogene Proteins v-erbB - metabolism</topic><topic>Organogenesis - genetics</topic><topic>Pharmacology</topic><topic>Phenotypes</topic><topic>Polarity</topic><topic>Protein-tyrosine kinase receptors</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Signal transduction</topic><topic>Signal Transduction - genetics</topic><topic>Signaling</topic><topic>Skin</topic><topic>Skin - embryology</topic><topic>Skin - metabolism</topic><topic>Skin diseases</topic><topic>Target recognition</topic><topic>Tumor suppressor genes</topic><topic>Tyrosine</topic><topic>Zebrafish</topic><topic>Zebrafish - embryology</topic><topic>Zebrafish - genetics</topic><topic>Zebrafish - metabolism</topic><topic>Zebrafish Proteins - genetics</topic><topic>Zebrafish Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Westcot, Stephanie E</creatorcontrib><creatorcontrib>Hatzold, Julia</creatorcontrib><creatorcontrib>Urban, Mark D</creatorcontrib><creatorcontrib>Richetti, Stefânia K</creatorcontrib><creatorcontrib>Skuster, Kimberly J</creatorcontrib><creatorcontrib>Harm, Rhianna M</creatorcontrib><creatorcontrib>Lopez Cervera, Roberto</creatorcontrib><creatorcontrib>Umemoto, Noriko</creatorcontrib><creatorcontrib>McNulty, Melissa S</creatorcontrib><creatorcontrib>Clark, Karl J</creatorcontrib><creatorcontrib>Hammerschmidt, Matthias</creatorcontrib><creatorcontrib>Ekker, Stephen C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Westcot, Stephanie E</au><au>Hatzold, Julia</au><au>Urban, Mark D</au><au>Richetti, Stefânia K</au><au>Skuster, Kimberly J</au><au>Harm, Rhianna M</au><au>Lopez Cervera, Roberto</au><au>Umemoto, Noriko</au><au>McNulty, Melissa S</au><au>Clark, Karl J</au><au>Hammerschmidt, Matthias</au><au>Ekker, Stephen C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protein-Trap Insertional Mutagenesis Uncovers New Genes Involved in Zebrafish Skin Development, Including a Neuregulin 2a-Based ErbB Signaling Pathway Required during Median Fin Fold Morphogenesis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-06-25</date><risdate>2015</risdate><volume>10</volume><issue>6</issue><spage>e0130688</spage><pages>e0130688-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Skin disorders are widespread, but available treatments are limited. A more comprehensive understanding of skin development mechanisms will drive identification of new treatment targets and modalities. Here we report the Zebrafish Integument Project (ZIP), an expression-driven platform for identifying new skin genes and phenotypes in the vertebrate model Danio rerio (zebrafish). In vivo selection for skin-specific expression of gene-break transposon (GBT) mutant lines identified eleven new, revertible GBT alleles of genes involved in skin development. Eight genes--fras1, grip1, hmcn1, msxc, col4a4, ahnak, capn12, and nrg2a--had been described in an integumentary context to varying degrees, while arhgef25b, fkbp10b, and megf6a emerged as novel skin genes. Embryos homozygous for a GBT insertion within neuregulin 2a (nrg2a) revealed a novel requirement for a Neuregulin 2a (Nrg2a)-ErbB2/3-AKT signaling pathway governing the apicobasal organization of a subset of epidermal cells during median fin fold (MFF) morphogenesis. In nrg2a mutant larvae, the basal keratinocytes within the apical MFF, known as ridge cells, displayed reduced pAKT levels as well as reduced apical domains and exaggerated basolateral domains. Those defects compromised proper ridge cell elongation into a flattened epithelial morphology, resulting in thickened MFF edges. Pharmacological inhibition verified that Nrg2a signals through the ErbB receptor tyrosine kinase network. Moreover, knockdown of the epithelial polarity regulator and tumor suppressor lgl2 ameliorated the nrg2a mutant phenotype. Identifying Lgl2 as an antagonist of Nrg2a-ErbB signaling revealed a significantly earlier role for Lgl2 during epidermal morphogenesis than has been described to date. Furthermore, our findings demonstrated that successive, coordinated ridge cell shape changes drive apical MFF development, making MFF ridge cells a valuable model for investigating how the coordinated regulation of cell polarity and cell shape changes serves as a crucial mechanism of epithelial morphogenesis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26110643</pmid><doi>10.1371/journal.pone.0130688</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-06, Vol.10 (6), p.e0130688 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1691276399 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | AKT protein Alleles Animal Fins - embryology Animal Fins - metabolism Animal genetic engineering Animals Biochemistry Breast cancer Cell size Cytology Danio rerio Developmental biology Disease Elongation Embryos ErbB protein ErbB-2 protein Gene expression Gene Expression Regulation, Developmental Genes Genetic aspects Genetics Genomics GRIP1 protein Insertional mutagenesis Integument Keratinocytes Kinases Larvae Localization Mammals Medical research Molecular biology Morphogenesis Mutagenesis Mutagenesis, Insertional Neuregulin Neuregulins - genetics Neuregulins - metabolism Oncogene Proteins v-erbB - genetics Oncogene Proteins v-erbB - metabolism Organogenesis - genetics Pharmacology Phenotypes Polarity Protein-tyrosine kinase receptors Proteins Proto-Oncogene Proteins c-akt - metabolism Signal transduction Signal Transduction - genetics Signaling Skin Skin - embryology Skin - metabolism Skin diseases Target recognition Tumor suppressor genes Tyrosine Zebrafish Zebrafish - embryology Zebrafish - genetics Zebrafish - metabolism Zebrafish Proteins - genetics Zebrafish Proteins - metabolism |
| title | Protein-Trap Insertional Mutagenesis Uncovers New Genes Involved in Zebrafish Skin Development, Including a Neuregulin 2a-Based ErbB Signaling Pathway Required during Median Fin Fold Morphogenesis |
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