title: Environmental and genetic modifiers of squint penetrance during zebrafish embryogenesis.
abstract: The Nodal-related subgroup of the TGFbeta superfamily of secreted cytokines regulates the specification of the mesodermal and endodermal germ layers during gastrulation. Two Nodal-related proteins - Squint (Sqt) and Cyclops (Cyc) - are expressed during germ-layer specification in zebrafish. Genetic sqt mutant phenotypes have defined a variable requirement for zygotic Sqt, but not for maternal Sqt, in midline mesendoderm development. However a comparison of phenotypes arising from oocytes or zygotes injected with Sqt antisense morpholinos has suggested a novel requirement for maternal Sqt in dorsal specification. In this study we examined maternal-zygotic mutants for each of two sqt alleles and we also compared phenotypes of closely related zygotic and maternal-zygotic sqt mutants. Each of these approaches indicated there is no general requirement for maternal Sqt. To better understand the dispensability of maternal and zygotic Sqt, we sought out developmental contexts that more rigorously demand intact Sqt signalling. We found that sqt penetrance is influenced by genetic modifiers, by environmental temperature, by levels of residual Activin-like activity and by Heat-Shock Protein 90 (HSP90) activity. Therefore, Sqt may confer an evolutionary advantage by protecting early-stage embryos against detrimental interacting alleles and environmental challenges.
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Wuhong
authors.initials: W
authors.lastname: Pei
authors.forename: P Huw
authors.initials: PH
authors.lastname: Williams
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Clark
authors.forename: Derek L
authors.initials: DL
authors.lastname: Stemple
authors.forename: Benjamin
authors.initials: B
authors.lastname: Feldman
mesh_terms: D028341:Activins / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004777:Environment; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D009154:Mutation; D055457:Nodal Protein; D055456:Nodal Signaling Ligands; D019683:Penetrance; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D015053:Zygote / Q000378:metabolism
chemical_list: D018841:HSP90 Heat-Shock Proteins; D055457:Nodal Protein; D055456:Nodal Signaling Ligands; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; C485171:ndr1 protein, zebrafish; D028341:Activins; D004247:DNA