p38a/Mapkapk2a signaling regulates tristetraprolin in the yolk syncytial layer: A role for mRNA degradation in the morphogenesis of a novel embryonic structure in vertebrate development

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dc.contributor.advisorWagner, Daniel S.en_US
dc.contributor.committeeMemberBartel, Bonnieen_US
dc.contributor.committeeMemberDiehl, Michael R.en_US
dc.contributor.committeeMemberGustin, Michael C.en_US
dc.contributor.committeeMemberSilberg, Jonathan J.en_US
dc.creatorGomez de la Torre Canny, Solen_US
dc.date.accessioned2014-08-26T21:25:03Zen_US
dc.date.available2015-05-01T05:01:02Zen_US
dc.date.created2014-05en_US
dc.date.issued2014-04-02en_US
dc.date.submittedMay 2014en_US
dc.date.updated2014-08-26T21:25:03Zen_US
dc.description.abstractThe yolk syncytial layer (YSL) is a novel embryonic structure that is unique to teleost fishes like the zebrafish. How existing genetic mechanisms can change to contribute to the generation of morphological novelties such as the YSL is a fundamental question of evolutionary biology. To address this question we examined the function of mapkapk2a (mk2a). Mk2a is required for YSL morphogenesis. To study the requirement of Mk2a signaling during embryogenesis, we analyzed the betty boop mutant (bbp). Bbp encodes Mk2a, the zebrafish homolog of mammalian MK2, a protein kinase activated by the p38 MAPK signaling pathway. bbp mutants display a striking lysis phenotype. bbp mutant embryos lose the expression of multiple YSL-specific genes. Thus, we examined the role of tristetraprolin (Ttp), a MK2 regulated mRNA-binding protein that promotes degradation of specific mRNA targets. Manipulation of the endogenous activity of Ttp showed that Ttp regulates the stability of YSL-specific mRNA molecules, most notably of mxtx2, which encodes for a zebrafish-specific transcription factor that activates a large proportion of YSL-specific genes. Specific activation of the Mk2a in the YSL inhibits Ttp activity in this cell layer, and prevents expression of Mxtx2 in other cells of the embryo. Expression of Mxtx2 or activation of the p38a /Mk2a pathway outside of the YSL results in dramatic defects in development. MK2 is not required for embryogenesis in mammals. Mutation of MK2 results in impaired inflammatory response and resistance to inflammatory diseases. The ability to manipulate the activity of the members of this conserved pathway in this novel context suggests that epiboly may be a useful platform to probe the molecular mechanism of TTP-dependent mRNA degradation that plays a crucial role in the regulation of the inflammatory response in mammals.en_US
dc.embargo.terms2015-05-01en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationGomez de la Torre Canny, Sol. "p38a/Mapkapk2a signaling regulates tristetraprolin in the yolk syncytial layer: A role for mRNA degradation in the morphogenesis of a novel embryonic structure in vertebrate development." (2014) Diss., Rice University. <a href="https://hdl.handle.net/1911/76727">https://hdl.handle.net/1911/76727</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/76727en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectYolk syncytial layeren_US
dc.subjectYSLen_US
dc.subjectZebrafishen_US
dc.subjectEpibolyen_US
dc.subjectMAPKAPK2en_US
dc.subjectMK2en_US
dc.subjectMk2aen_US
dc.subjectP38 MAPKen_US
dc.subjectP38aen_US
dc.subjectMapk14en_US
dc.subjectTristetraprolinen_US
dc.subjectTTPen_US
dc.subjectZFP36en_US
dc.subjectMxtx2en_US
dc.subjectMAPK signalingen_US
dc.subjectEmbryogenesisen_US
dc.titlep38a/Mapkapk2a signaling regulates tristetraprolin in the yolk syncytial layer: A role for mRNA degradation in the morphogenesis of a novel embryonic structure in vertebrate developmenten_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentBiochemistry and Cell Biologyen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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