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Eukaryotic Cell, March 2005, p. 526-535, Vol. 4, No. 3
1535-9778/05/$08.00+0     doi:10.1128/EC.4.3.526-535.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Sex-Specific Homeodomain Proteins Sxi1{alpha} and Sxi2a Coordinately Regulate Sexual Development in Cryptococcus neoformans

Christina M. Hull,1,{dagger} Marie-Josee Boily,1 and Joseph Heitman1,2*

Department of Molecular Genetics and Microbiology,1 the Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina2

Received 14 January 2005/ Accepted 14 January 2005

Homeodomain proteins are central regulators of development in eukaryotes. In fungi, homeodomain proteins have been shown to control cell identity and sexual development. Cryptococcus neoformans is a human fungal pathogen with a defined sexual cycle that produces spores, the suspected infectious particles. Previously, only a single homeodomain regulatory protein involved in sexual development, Sxi1{alpha}, had been identified. Here we present the discovery of Sxi2a, a predicted but heretofore elusive cell-type-specific homeodomain protein essential for the regulation of sexual development. Our studies reveal that Sxi2a is necessary for proper sexual development and sufficient to drive this development in otherwise haploid {alpha} cells. We further show that Sxi1{alpha} and Sxi2a interact with one another and impart similar expression patterns for two key mating genes. The discovery of Sxi2a and its relationship with Sxi1{alpha} leads to a new model for how the sexual cycle is controlled in C. neoformans, with implications for virulence.

* Corresponding author. Mailing address: 322 CARL Building, Box 3546, Department of Molecular Genetics and Microbiology, 100 Research Dr., Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-2824. Fax: (919) 684-5458. E-mail: heitm001{at}duke.edu.

{dagger} Present address: Departments of Biomolecular Chemistry and Medical Microbiology & Immunology, University of Wisconsin—Madison, Madison, WI 53706.

Eukaryotic Cell, March 2005, p. 526-535, Vol. 4, No. 3
1535-9778/05/$08.00+0     doi:10.1128/EC.4.3.526-535.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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