The second life of Plasmodium in the mosquito host: gene regulation on the move

Malaria parasites face dynamically changing environments and strong selective constraints within human and mosquito hosts. To survive such hostile and shifting conditions, Plasmodium switches transcriptional programs during development and has evolved mechanisms to adjust its phenotype through heterogeneous patterns of gene expression. In vitro studies on culture-adapted isolates have served to set the link between chromatin structure and functional gene expression. Yet, experimental evidence is limited to certain stages of the parasite in the vertebrate, i.e. blood, while the precise mechanisms underlying the dynamic regulatory landscapes during development and in the adaptation to within-host conditions remain poorly understood. In this review, we discuss available data on transcriptional and epigenetic regulation in Plasmodium mosquito stages in the context of sporogonic development and phenotypic variation, including both bet-hedging and environmentally triggered direct transcriptional responses. With this, we advocate the mosquito offers an in vivo biological model to investigate the regulatory networks, transcription factors and chromatin-modifying enzymes and their modes of interaction with regulatory sequences, which might be responsible for the plasticity of the Plasmodium genome that dictates stage- and cell type-specific blueprints of gene expression.