title: aldh7a1 regulates eye and limb development in zebrafish.
abstract: Uveal coloboma is a potentially blinding congenital ocular malformation caused by failure of the optic fissure to close during development. Although mutations in numerous genes have been described, these account for a minority of cases, complicating molecular diagnosis and genetic counseling. Here we describe a key role of aldh7a1 as a gene necessary for normal eye development. We show that morpholino knockdown of aldh7a1 in zebrafish causes uveal coloboma and misregulation of nlz1, another known contributor to the coloboma phenotype, as well as skeletal abnormalities. Knockdown of aldh7a1 leads to reduced cell proliferation in the optic cup of zebrafish, delaying the approximation of the edges of the optic fissure. The aldh7a1 morphant phenotype is partially rescued by co-injection of nlz1 mRNA suggesting that nlz1 is functionally downstream of aldh7a1 in regulating cell proliferation in the optic cup. These results support a role of aldh7a1 in ocular development and skeletal abnormalities in zebrafish.
authors.affiliation: Unit on Pediatric, Developmental and Genetic Ophthalmology, Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Holly E
authors.initials: HE
authors.lastname: Babcock
authors.affiliation: Unit on Pediatric, Developmental and Genetic Ophthalmology, Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Sunit
authors.initials: S
authors.lastname: Dutta
authors.affiliation: Unit on Pediatric, Developmental and Genetic Ophthalmology, Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Ramakrishna P
authors.initials: RP
authors.lastname: Alur
authors.affiliation: Molecular Toxicology and Environmental Health Sciences Program, Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Chad
authors.initials: C
authors.lastname: Brocker
authors.affiliation: Molecular Toxicology and Environmental Health Sciences Program, Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Vasiliou
authors.affiliation: Division of Biostatistic & Epidemiology, Clinical Trials Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Susan
authors.initials: S
authors.lastname: Vitale
authors.affiliation: Immunopathology Section, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Mones
authors.initials: M
authors.lastname: Abu-Asab
authors.affiliation: Unit on Pediatric, Developmental and Genetic Ophthalmology, Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Brooks
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000818:Animals; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000235:genetics; D005121:Extremities / Q000196:embryology*; D005123:Eye / Q000196:embryology / Q000378:metabolism*; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D010641:Phenotype; D014212:Tretinoin / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D029961:Zebrafish Proteins; C435747:znf703 protein, zebrafish; D014212:Tretinoin; D000444:Aldehyde Dehydrogenase