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PLoS Genet

Title:		Genetic circuits that govern bisexual and unisexual reproduction in Cryptococcus neoformans
Author(s):		Feretzaki M; Heitman J;
Address:		"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America"
Journal Title:		PLoS Genet
Year:		2013
Volume:		20130815
Issue:		8
Page Number:		e1003688 -
DOI:		10.1371/journal.pgen.1003688
ISSN/ISBN:		1553-7404 (Electronic) 1553-7390 (Print) 1553-7390 (Linking)
Abstract:		"Cryptococcus neoformans is a human fungal pathogen with a defined sexual cycle. Nutrient-limiting conditions and pheromones induce a dimorphic transition from unicellular yeast to multicellular hyphae and the production of infectious spores. Sexual reproduction involves cells of either opposite (bisexual) or one (unisexual) mating type. Bisexual and unisexual reproduction are governed by shared components of the conserved pheromone-sensing Cpk1 MAPK signal transduction cascade and by Mat2, the major transcriptional regulator of the pathway. However, the downstream targets of the pathway are largely unknown, and homology-based approaches have failed to yield downstream transcriptional regulators or other targets. In this study, we applied insertional mutagenesis via Agrobacterium tumefaciens transkingdom DNA delivery to identify mutants with unisexual reproduction defects. In addition to elements known to be involved in sexual development (Crg1, Ste7, Mat2, and Znf2), three key regulators of sexual development were identified by our screen: Znf3, Spo11, and Ubc5. Spo11 and Ubc5 promote sporulation during both bisexual and unisexual reproduction. Genetic and phenotypic analyses provide further evidence implicating both genes in the regulation of meiosis. Phenotypic analysis of sexual development showed that Znf3 is required for hyphal development during unisexual reproduction and also plays a central role during bisexual reproduction. Znf3 promotes cell fusion and pheromone production through a pathway parallel to and independent of the pheromone signaling cascade. Surprisingly, Znf3 participates in transposon silencing during unisexual reproduction and may serve as a link between RNAi silencing and sexual development. Our studies illustrate the power of unbiased genetic screens to reveal both novel and conserved circuits that operate sexual reproduction"
Keywords:		"Cell Fusion Cryptococcus neoformans/*genetics Diploidy Fungal Proteins/*genetics *Genes, Mating Type, Fungal Humans Hyphae/genetics Meiosis Mitogen-Activated Protein Kinase Kinases/genetics/metabolism Pheromones/genetics Reproduction/*genetics Signal Tran;"
Notes:		"MedlineFeretzaki, Marianna Heitman, Joseph eng R01 AI039115/AI/NIAID NIH HHS/ R37 AI039115/AI/NIAID NIH HHS/ NIH R37 AI39115/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural 2013/08/24 PLoS Genet. 2013; 9(8):e1003688. doi: 10.1371/journal.pgen.1003688. Epub 2013 Aug 15"