title: The lineage-specific gene ponzr1 is essential for zebrafish pronephric and pharyngeal arch development.
abstract: The Homeobox (Hox) and Paired box (Pax) gene families are key determinants of animal body plans and organ structure. In particular, they function within regulatory networks that control organogenesis. How these conserved genes elicit differences in organ form and function in response to evolutionary pressures is incompletely understood. We molecularly and functionally characterized one member of an evolutionarily dynamic gene family, plac8 onzin related protein 1 (ponzr1), in the zebrafish. ponzr1 mRNA is expressed early in the developing kidney and pharyngeal arches. Using ponzr1-targeting morpholinos, we show that ponzr1 is required for formation of the glomerulus. Loss of ponzr1 results in a nonfunctional glomerulus but retention of a functional pronephros, an arrangement similar to the aglomerular kidneys found in a subset of marine fish. ponzr1 is integrated into the pax2a pathway, with ponzr1 expression requiring pax2a gene function, and proper pax2a expression requiring normal ponzr1 expression. In addition to pronephric function, ponzr1 is required for pharyngeal arch formation. We functionally demonstrate that ponzr1 can act as a transcription factor or co-factor, providing the first molecular mode of action for this newly described gene family. Together, this work provides experimental evidence of an additional mechanism that incorporates evolutionarily dynamic, lineage-specific gene families into conserved regulatory gene networks to create functional organ diversity.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Bedell
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Person
authors.forename: Jon D
authors.initials: JD
authors.lastname: Larson
authors.forename: Anna
authors.initials: A
authors.lastname: McLoon
authors.forename: Darius
authors.initials: D
authors.lastname: Balciunas
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Clark
authors.forename: Kevin I
authors.initials: KI
authors.lastname: Neff
authors.forename: Katie E
authors.initials: KE
authors.lastname: Nelson
authors.forename: Brent R
authors.initials: BR
authors.lastname: Bill
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Schimmenti
authors.forename: Soraya
authors.initials: S
authors.lastname: Beiraghi
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Ekker
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D005075:Biological Evolution; D015415:Biomarkers / Q000378:metabolism; D001934:Branchial Region / Q000196:embryology* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D007668:Kidney / Q000033:anatomy & histology; D009024:Morphogenesis / Q000502:physiology; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D060910:Pronephros / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000033:anatomy & histology* / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051762:PAX2 Transcription Factor; D014157:Transcription Factors; D029961:Zebrafish Proteins; C497320:pax2a protein, zebrafish