{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"Conservation and Evolutionary \nDivergence in the Activity of Receptor-regulated Smads","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/11401/71418"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"Activity of the TGF\u0392 pathway is essential to the establishment of \nbody axes and tissue differentiation in bilaterians. Orthologs for core pathway members have \nbeen found in all metazoans. Uncertain homology of the body axes and tissues patterned by \nthis pathway raises questions about the activities of these molecules across the metazoan \ntree. We focus on the principal canonical transduction proteins (R-Smads) of the TGF\u0392 \npathway, which instruct both axial patterning and tissue differentiation in the developing \nembryo. We compare the activity of R-Smads from a cnidarian (Nematostella vectensis), an \narthropod (Drosophila melanogaster), and a vertebrate (Xenopus laevis) in Xenopus embryonic \nassays.  NvSmad1/5 ventralized Xenopus embryos when expressed in dorsal blastomeres, similar \nto the effects of XSmad1. However, NvSmad1/5 was less potent than XSmad1 in its ability to \nactivate downstream target genes in Xenopus animal cap assays. NvSmad2/3 strongly induced \ngeneral mesendoderm markers, but weakly induced genes involved in specifying the Spemann \norganizer. Furthermore, NvSmad2/3 was unable to induce a secondary axis in Xenopus embryos, \nwhereas the orthologs from Xenopus (XSmad2 and XSmad2) and Drosophila (dSmad2) were capable \nof doing so. Replacement of the NvSmad2/3 MH2 domain with the Xenopus counterpart led to a \nslight increase in inductive capability, but it could not generate a secondary body axis.  We \nconclude that the activities of Smad1/5 orthologs have been largely conserved across Metazoa, \nbut the activity of Smad2/3 orthologs has undergone more evolutionary divergence. Given the \nhigh level of sequence identity among R-Smad orthologs, we compared the protein sequences of \nSmad2/3 orthologs from 30 different metazoan taxa to locate regions of variation among taxa. \nFunctional regions showed striking conservation, with most of the amino acid variation \nlocated in regions that are not well-described in the literature at present. We recommend \nfurther chimeric and mutagenic experimentation with Smad2/3 and present candidate sites. Our \ndata demonstrate that large-scale morphological variation can be caused by fine-scale \nmolecular divergence."},{"label":"dcterms.available","value":"2015-04-24T14:47:29Z"},{"label":"dcterms.contributor","value":"O'Leary, Maureen A, Thomsen, Gerald H"},{"label":"dcterms.creator","value":"Sorrentino, Gina"},{"label":"dcterms.dateAccepted","value":"2013-05-22T17:35:37Z"},{"label":"dcterms.dateSubmitted","value":"2015-04-24T14:47:29Z"},{"label":"dcterms.description","value":"Department \nof Anatomical Sciences"},{"label":"dcterms.extent","value":"130 pg."},{"label":"dcterms.format","value":"Monograph"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/11401/71418"},{"label":"dcterms.issued","value":"2012-05-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2015-04-24T14:47:29Z (GMT). No. of bitstreams: 3\nSorrentino_grad.sunysb_0771E_10913.pdf.jpg: 1894 bytes, checksum: a6009c46e6ec8251b348085684cba80d (MD5)\nSorrentino_grad.sunysb_0771E_10913.pdf.txt: 217531 bytes, checksum: 6257feeba4bf37a268852107942dc984 (MD5)\nSorrentino_grad.sunysb_0771E_10913.pdf: 15031859 bytes, checksum: 7b49e1ab08ce5fbeac51afae4967a6b3 (MD5)\n  Previous issue date:    1"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"Evolution & development"},{"label":"dcterms.title","value":"Conservation and Evolutionary \nDivergence in the Activity of Receptor-regulated Smads"},{"label":"dcterms.type","value":"Dissertation"},{"label":"dc.type","value":"Dissertation"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/15%2F47%2F67%2F154767369879752813077646657277716920013/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/15%2F47%2F67%2F154767369879752813077646657277716920013","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}