Somatic cells regulation of maternal mRNA translation in mammalian oocytes
The final phase of oocyte differentiation, fertilization and early embryo development occur in absence of transcription, thus cell cycle progression and genome reprogramming rely on translation of stored mRNAs, until the activatio...
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Descripción del proyecto
The final phase of oocyte differentiation, fertilization and early embryo development occur in absence of transcription, thus cell cycle progression and genome reprogramming rely on translation of stored mRNAs, until the activation of embryo genome. Objective of the present study is to analyze the pathways that regulate translation during oocyte-to-embryo transition. We propose the follicular cells to play a role in this process. Though it is known that intercellular bi-directional communications are essential to coordinate oogenesis with folliculogenesis, the involvement of somatic cells in the regulation of translation is a new concept. Our study will be conducted in mice (outgoing phase) and cows (return phase) since their embryo genome activation follows divergent dynamics: early 2-cell stage in mice, 8-16 cells in cows. The study will aim to: 1) understand how somatic cells regulate the activation of selected mRNA translation in oocytes; 2) determine if a mis-regulation of mRNA translation accounts for impaired embryo development during reproductive aging; 3) identify the extent to which these mechanisms are evolutionarily conserved in mammals. Different strategies will be adopted in order to knock-down the putative pathways, from pharmacological inhibition to RNA interference techniques and genetic models, when available. The translation activity will be investigated by innovative approaches as the use of luciferase reporters.
While aiming to uncover some of the yet poorly known mechanisms that drive a highly differentiated cell as the oocyte to the perfect totipotent cell, this project represents the opportunity for a European researcher at the crucial transition to become independent to work with leading edge scientists and advanced technologies in the field of cell signaling and reproductive sciences. The return phase will allow the transfer of knowledge and the establishment of networks of international cooperation.