Respuesta Regenerativa Glial en el disco imaginal de ojo de Drosophila melanogaster

Abstract

Tissue and organ regeneration is a capacity of many organisms that occurs under different thresholds and at different stages of development. Some of the organisms that exhibit a greater ability to reconstruct damaged structures have been used as system models. However, the experimental analysis of the processes that underlie tissue regeneration is often limited, in part because compared with other organisms the genetic manipulation techniques available in most of the organism with high regenerative ability are scarce (planaria, hydras and amphibians, among others). The imaginal discs of Drosophila melanogaster are an excellent model system to discover evolutionary conserved gene function and gene networks. Considering the prevalent conservation of gene function, the results obtained in Drosophila have recurrently had important implications for human health. This insect has been also used to study the mechanisms involved in organ regeneration. More specifically, the imaginal eye disc allows us to analyze the homeostatic responses that occur when the nervous system is damaged. The nervous cells that form the eye discs have an origin independent of the CNS, this allows us to analyze the consequences of the ablation of a part of the tissue, avoiding the lethality caused when the CNS is damaged. In this thesis, we have used conditional gene expression systems to induce damage in the neurogenic region of the eye disc and thus examined the cellular processes involved in nervous system repair. Our results have allowed us to identify characteristic features of a regenerative response, such as: the activation of compensatory proliferation and the reconstruction of damaged tissue. One of the consequences of the damage in the neuronal tissue is the activation of glial cells that can mediate the structural remodeling of the nervous tissue. This type of cells play a critical role during the development of the nervous system, and its function is central during the processes of nerve regeneration. The unique features of the eye disc development is an ideal model to study the mechanisms activated during the glial regenerative response. In the eye disc, the glial cells are specified in the optic nerve and then they have to migrate to the disc region. During the migration process glial cells divide. Both cellular processes are regulated by signals that emanate from the eye discs region. Therefore, these signals must function at a long distance. Using our conditional systems to induce damage, we have injured the neurogenic region of the eye and analyzed the behavior of the glial cells. We have found that damage promotes a glial regenerative response that consists of an increase in migration and glial division, and the induction of phagocytic activity of some glia. In addition, we have discovered that Hh and Dpp signaling pathways function simultaneously to induce the proliferation of glial cells in the retina and to activate the JNK pathway for facilitating glial migration.