Commitment to differentiation and cell cycle re-entry are coincident but separable events in the transformation of African trypanosomes from their bloodstream to their insect form

Abstract

African trypanosomes undergo extensive changes in cellular morphology, biochemistry and surface antigen expression as they differentiate from their bloodstream form to those forms that colonise the midgut of their tsetse fly vector. If initiated with stumpy-form cells, a non-dividing sub-type of the bloodstream parasite, differentiation and cell cycle re-entry occur synchronously in the population and provide a means to dissect the respective controls of proliferation and transformation. We have exploited this synchrony to determine the respective importance and hierarchy of the known triggers for differentiation (cis aconitate, temperature drop) for individual components of both differentiation and the cell cycle. This has revealed the pre-eminence of cis aconitate as a primary trigger for parasite differentiation, and has allowed us to determine that the cellular commitment to both differentiation and cell-cycle re-entry are precisely co-incident processes.