Cell identity and sexual development in Cryptococcus neoformans are controlled by the mating-type-specific homeodomain protein Sxi1α

Virulence in the human fungal pathogen Cryptococcus neoformans is associated with the alpha mating type. Studies to identify the properties of et cells that enhance pathogenesis have led to the identification of a mating-type locus of unusually large size and distinct architecture. Here, we demonstrate that the previously identified MATalpha components are insufficient to regulate sexual differentiation, and we identify a novel alpha-specific regulator, SXI1alpha. Our data show that SXI1alpha establishes alpha cell identity and controls progression through the sexual cycle, and we discover that ectopic expression of SXI1alpha in a cells is sufficient to drive a/alpha sexual development. SXI1alpha is the first example of a key regulator of cell identity and sexual differentiation in C. neoformans, and its identification and characterization lead to a new model of how cell fate and the sexual cycle are controlled in C. neoformans.