Investigations of potential roles of hypoxic response genes in Drosophila primordial germ cell development.

摘要

The cellular responses that allow a cell to survive and adapt to hypoxic stress (low oxygen) are largely conserved. The Hypoxia-Inducible Factor transcription factors (HIFs) are the primary transcription factors mediating responses to hypoxic stress. HIFs are composed of alpha and beta subunits. HIF-alpha is only stable in hypoxic conditions. The pathway for oxygen-dependent degradation of HIF-alpha includes a prolyl-hydroxylase (PHD) and the VHL E3 ligase. The Drosophila homlogs of HIF-alpha, HIF-beta, PHD, and VHL are encoded by the similar, tango, fatiga/Hph, and Vhl genes, respectively. Previous studies have demonstrated that similar has roles in Drosophila tracheal development as well as border cell migration. Here I have used the development of germ cells in Drosophila as a tool to study the effects of low oxygen stress, and to explore the potential roles of hypoxic response genes in germ cell development. Utilizing low oxygen culture conditions and loss-of-function mutants I have observed that Drosophila embryogenesis is sensitive to oxygen tension and the zygotic loss of Drosophila HIF-1alpha is not sufficient to induce primordial germ cell defects. Further examination of the complete loss-of-function of other Drosophila HIF components, such as fatiga, could reveal whether it is the HIF hypoxic response pathway or a HIF independent hypoxia induced pathway that mediates Drosophila primordial germ cell development in wild-type embryos exposed to hypoxic conditions.