Análisis celular y genético del proceso de fusión y expansión de histoblastos durante la metamorfosis de drosophila

• Autores: Nikolay Ninov
• Directores de la Tesis: Enrique Martín Blanco (dir. tes.)
• Lectura: En la Universitat de Barcelona ( España ) en 2008
• Idioma: español
• Tribunal Calificador de la Tesis: Antonio García-Bellido y García de Diego (presid.), Florenci Serras Rigalt (secret.), Markus Affolter (voc.), Emilli Saló (voc.), Franck Pichaud (voc.)
• Materias:
  • Ciencias de la vida
    • Genética
      • Embriología
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• Resumen

  • The expansion and joining of epithelial sheets represent a fundamental morphogenetic event known as Epithelial Fusion, which participates in the sealing of multiple organs and tissues in vertebrates and is also essential for wound healing. Much of the present knowledge regarding the cellular and molecular mechanisms of epithelial fusion comes from Dorsal Closure in Drosophila and Ventral Enclosure in C.elegans, two models where epithelial morphogenesis takes place in the absence of cell proliferation. Being important to analyse cell sheet expansion associated with cell cycle control, we use the development of the adult epidermis of Drosophila as a model to analyse the cellular and genetic mechanism controlling epithelial expansion coupled to cell proliferation. The adult epidermis is formed, by adult precursor cells called histoblasts, which proliferate, expand and displace the larval epidermal cells during Metamorphosis. We concentrated on analysing the cell cycle control of histoblast proliferation, the cellular and signalling control of histoblast expansion and the mechanism involved in the elimination of larval epidermal cells. We find that the cell cycle of histoblasts is dynamically regulated at three stages of development. In larval stages, histoblasts grow in size but do not divide. Signalling by Pi3K is necessary for cell growth at this stage. In addition histoblasts store a reservoir of the G1 regulator Cyclin E. At the onset of Metamorphosis, the proliferation of histoblasts is triggered by a pulse of Ecdysone, which activates the cell cycle by stimulating the transcription of string. By taking advantage of the reservoir of Cyclin E, histoblast undergo three fast divisions with unconventional phasing of the cell cycles (G2/M/S). After the larval pool of Cyclin E becomes consumed, histoblasts enter in a second stage where the cell cycle is slower and is coupled to G1. During the second stage histoblasts require metabolic activity mediated by Pi3K and mitogen input from the EGFR pathway for cell cycle progression. During the second stage of proliferation, histoblast begin the invasion of the larval epidermis by collective cellular motility of peripheral histoblasts and actin rich cellular extensions. By conducting a screen for potential signalling pathways involved in the motility of histoblasts, we identified that signalling by Dpp is necessary for invasion, enforcing actin dynamics and changes in cell adhesion. During the expansion of the histoblasts, larval cells are eliminated by apical constriction mediated by myosin contractility and engulfment by macrophages. The death of larval cells is triggered autonomously by Ecdysone, but is positively influenced by the expansion and proliferation of the histoblasts.