Control of developmental transitions by OCT4: a new role as a regulator of mTOR activity at gastrulation
- Autores: Antonio Barral
- Directores de la Tesis: Miguel Manzanares Fourcade (dir. tes.)
- Lectura: En la Universidad Autónoma de Madrid ( España ) en 2023
- Idioma: español
- Número de páginas: 152
- Enlaces
- Tesis en acceso abierto en: Biblos-e Archivo
- Resumen
A key player during embryonic development, the transcription factor OCT4, has been widely studied in the context of pluripotency, where it is essential for its acquisition and maintenance, both in vivo and in tissue culture. Nevertheless, in recent years, there has been some effort devoted to the study of this factor in a much different context, that of gastrulation. Certainly, after implantation of the mouse embryo, while pluripotency is disappearing and its cells are already beginning to be specified to particular lineages, OCT4 is still expressed.
Here, we have attempted to uncover previously unknown roles of OCT4 during gastrulation. By analyzing transcriptomic datasets previously published by others and us, and using tissue culture (namely embryonic stem cells, embryonic fibroblasts, and gastruloids) as well as in vivo (gastrulating embryos) experimental approaches, we found that OCT4 is repressing the mTOR pathway, most possibly through the induction of two negative regulators –Deptor and Bnip3. The mTOR pathway, mainly explored in the context of disease, is one of the most relevant integrators of cellular signaling, which controls numerous biosynthetic processes as well as supporting cell growth and proliferation. Its specific functions during embryo development, however, have been less studied, although mounting evidence points to a contribution of mTOR to cell fate acquisition. In this framework, our work strongly suggests that the existence of an OCT4-mTOR regulatory axis is relevant in the postimplantation mouse embryo, and necessary to trigger an early primitive streak signature at the onset of gastrulation
