Plasmodium, the causative agent of malaria, has to undergo sexual 
differentiation and development in anopheline mosquitoes for transmission to 
occur. To isolate genes specifically induced in both organisms during the early 
stages of Plasmodium differentiation in the mosquito, two cDNA libraries were 
constructed, one enriched for sequences expressed in differentiating Plasmodium 
berghei ookinetes and another enriched for sequences expressed in Anopheles 
stephensi guts containing invading ookinetes and early oocysts. Sequencing of 
457 ookinete library clones and 652 early oocyst clones represented 175 and 346 
unique expressed sequence tags, respectively. Nine of 13 Plasmodium and four of 
the five Anopheles novel expressed sequence tags analyzed on Northern blots were 
induced during ookinete differentiation and mosquito gut invasion. Ancaspase-7, 
an Anopheles effector caspase, is proteolytically activated during Plasmodium 
invasion of the midgut. WARP, a gene encoding a Plasmodium surface protein with 
a von Willebrand factor A-like adhesive domain, is expressed only in ookinetes 
and early oocysts. An anti-WARP polyclonal antibody strongly inhibits (70-92%) 
Plasmodium development in the mosquito, making it a candidate antigen for 
transmission blocking vaccines. The present results and those of an accompanying 
report (Srinivasan, P., Abraham, E. G., Ghosh, A. K., Valenzuela, J., Ribeiro, 
J. M. C., Dimopoulos G., Kafatos, F. C., Adams, J. H., and Jacobs-Lorena, M. 
(2004) J. Biol. Chem. 279, 5581-5587) provide the foundation for further 
analysis of Plasmodium differentiation in the mosquito and of mosquito responses 
to the parasite.