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dc.contributor.advisorCraig C. Mello
dc.contributor.authorKim, Soyoung
dc.date2022-08-11T08:08:42.000
dc.date.accessioned2022-08-23T16:04:32Z
dc.date.available2022-08-23T16:04:32Z
dc.date.issued2008-05-23
dc.date.submitted2008-10-29
dc.identifier.doi10.13028/qqty-w565
dc.identifier.urihttp://hdl.handle.net/20.500.14038/31707
dc.description.abstractAsymmetric cell divisions constitute a basic foundation of animal development, providing a mechanism for placing specific cell types at defined positions in a developing organism. In a 4-cell stage embryo in Caenorhabditis elegansthe EMS cell divides asymmetrically to specify intestinal cells, which requires a polarizing signal from the neighboring P2 cell. Here we describe how the extracellular signal from P2 is transmitted from the membrane to the nucleus during asymmetric EMS cell division, and present the identification of additional components in the pathways that accomplish this signaling. P2/EMS signaling involves multiple inputs, which impinge on the Wnt, MAPK-like, and Src pathways. Transcriptional outputs downstream of these pathways depend on a homolog of β-catenin, WRM-1. Here we analyze the regulation of WRM-1, and show that the MAPK-like pathway maintains WRM-1 at the membrane, while its release and nuclear translocation depend on Wnt/Src signaling and sequential phosphorylation events by the major cell-cycle regulator CDK-1 and by the membrane-bound GSK-3 during EMS cell division. Our results provide novel mechanistic insights into how the signaling events at the cortex are coupled to the asymmetric EMS cell division through WRM-1. To identify additional regulators in the pathways governing gut specification, we performed suppressor genetic screens using temperature-sensitive alleles of the gutless mutant mom-2/Wnt, and extra-gut mutant cks-1. Five intragenic suppressors and three semi-dominant suppressors were isolated in mom-2 suppressor screens. One extragenic suppressor was mapped to the locus ifg-1, eukaryotic translation initiation factor eIF4G. From the suppressor screen using cks-1(ne549), an allele of the self-cleaving nucleopore protein npp-10 was identified as a suppressor of cks-1(ne549)and other extra-gut mutants. Taken together, these results help us better understand how the fate of intestinal cells are specified and regulated in early C. elegans embryos and broaden our knowledge of cell polarity and fate specification.
dc.language.isoen_US
dc.rightsCopyright is held by the author, with all rights reserved.
dc.subjectCell Polarity
dc.subjectCaenorhabditis elegans Proteins
dc.subjectCytoskeletal Proteins
dc.subjectBody Patterning
dc.subjectCell Differentiation
dc.subjectDigestive System
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectAnimal Experimentation and Research
dc.subjectCells
dc.subjectDigestive System
dc.subjectEmbryonic Structures
dc.titleA Study of Cell Polarity and Fate Specification in Early <em>C. Elegans</em> Embryos: A Dissertation
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1385&amp;context=gsbs_diss&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/385
dc.legacy.embargo2017-04-24T00:00:00-07:00
dc.identifier.contextkey658031
refterms.dateFOA2022-08-26T04:57:02Z
html.description.abstract<p>Asymmetric cell divisions constitute a basic foundation of animal development, providing a mechanism for placing specific cell types at defined positions in a developing organism. In a 4-cell stage embryo in <em>Caenorhabditis elegans</em>the EMS cell divides asymmetrically to specify intestinal cells, which requires a polarizing signal from the neighboring P2 cell. Here we describe how the extracellular signal from P2 is transmitted from the membrane to the nucleus during asymmetric EMS cell division, and present the identification of additional components in the pathways that accomplish this signaling.</p> <p>P2/EMS signaling involves multiple inputs, which impinge on the Wnt, MAPK-like, and Src pathways. Transcriptional outputs downstream of these pathways depend on a homolog of β-catenin, WRM-1. Here we analyze the regulation of WRM-1, and show that the MAPK-like pathway maintains WRM-1 at the membrane, while its release and nuclear translocation depend on Wnt/Src signaling and sequential phosphorylation events by the major cell-cycle regulator CDK-1 and by the membrane-bound GSK-3 during EMS cell division. Our results provide novel mechanistic insights into how the signaling events at the cortex are coupled to the asymmetric EMS cell division through WRM-1.</p> <p>To identify additional regulators in the pathways governing gut specification, we performed suppressor genetic screens using temperature-sensitive alleles of the gutless mutant <em>mom-2/Wnt</em>, and extra-gut mutant <em>cks-1</em>. Five intragenic suppressors and three semi-dominant suppressors were isolated in <em>mom-2</em> suppressor screens. One extragenic suppressor was mapped to the locus <em>ifg-1</em>, eukaryotic translation initiation factor <em>eIF4G</em>. From the suppressor screen using <em>cks-1(ne549)</em>, an allele of the self-cleaving nucleopore protein <em>npp-10</em> was identified as a suppressor of <em>cks-1(ne549)</em>and other extra-gut mutants.</p> <p>Taken together, these results help us better understand how the fate of intestinal cells are specified and regulated in early <em>C. elegans</em> embryos and broaden our knowledge of cell polarity and fate specification.</p>
dc.identifier.submissionpathgsbs_diss/385
dc.contributor.departmentRNA Therapeutics Institute
dc.description.thesisprogramInterdisciplinary Graduate Program


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