Busqueda de marcadores y mediadores de competición celular
Author
López-Gay Orts, Jesús MaríaAdvisor
Moreno, EduardoEntity
UAM. Departamento de Biología Molecular; Centro Nacional de Investigaciones Oncológicas (CNIO)Date
2010-05-12Subjects
Marcadores biológicos-Tesis doctorales; Apoptosis-Tesis doctorales; Biología y Biomedicina / BiologíaNote
Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 12-05-2010Abstract
Cell competition is a process of non-autonomous cell death induction which permits the elimination of less fit cells from a tissue. Although cell competition is extensively described in Drosophila melanogaster, the lack of specific molecular markers makes difficult the study of this process in other model systems. Cell competition may have the capacity to control cellular processes during development or in the context of pathogenesis; however, its exact role remains to be uncovered. In this work, there are proposed eight specific markers of cell competition: amalgam, tms1, contactin, gustavus, CG6151, fu2, CG3305 and CG11165. One of these genes – CG6151/maxwell’s demon (mwd) – codes for a transmembrane protein and has three protein isoforms that differ in their C-terminal end. The varying C-terminal end faces the intercellular space, thus enabling possible communication between competing cells. While one of these isoforms – Mwd ubi – is expressed ubiquitously in wild-type wing imaginal discs, the other two isoforms – Mwd LoseA and Mwd LoseB – are expressed specifically in the “loser” cells in situations of cell competition. In accordance, each type of isoform has a distinct role in cell survival; whereas, the presence of Mwd ubi is necessary for cell survival in a non-autonomous way, the artificial depletion of Mwd LoseA/B in the loser cells inhibits their competitive elimination. Moreover, the overexpression of the Mwd LoseA/B isofoms in wild-type cells is sufficient to induce their cell death, thus mimicking cell competition. Another possible marker of cell competition analyzed here is fu2. fu2 codes for a zinc finger transcription factor. An increase of fu2 expression is also observed in the loser cells during cell competition. Knock-down of Fu2 specifically in the loser cells prevents their elimination. Being a transcription factor, Fu2 could modulate the expression of some other genes during cell competition. The present work exposes the search of several of these Fu2 target genes. In summary, the aim of this study is to give new tools to the scientific community that could serve to clarify the role of cell competition during development, aging or cancer.
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"Texto de la Tesis Doctoral"
Google Scholar:López-Gay Orts, Jesús María
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