Epistatic genetic interactions govern morphogenesis during sexual reproduction and infection in a global human fungal pathogen

Abstract

Significance Cellular development is regulated by a complex web of signaling pathways that respond to both intracellular and extracellular cues. Morphological transitions in pathogenic fungi, such as those observed during sexual reproduction or in response to the host environment, offer tractable models for understanding the principles that govern eukaryotic cell development and morphogenesis. Using the human fungal pathogen Cryptococcus deneoformans as a model and applying quantitative trait locus analysis, we defined genes and gene–gene interactions involved in the yeast–hyphal transition and titanization, two morphological developments that are important for adaptation, pathogenesis, and evolution of this fungal pathogen. Our study highlights the conservation and complexity of key signaling pathways in regulating cell development in fungi, as well as other eukaryotes.