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Sexual Development in Cryptococcus neoformans Requires CLP1, a Target of the Homeodomain Transcription Factors Sxi1 and Sxi2a

Joanne L. Ekena,¹ Brynne C. Stanton,¹ Jessica A. Schiebe-Owens,^2, and Christina M. Hull^1,2*

Department of Biomolecular Chemistry,¹ Department of Medical Microbiology & Immunology, University of Wisconsin, School of Medicine and Public Health, Madison, Wisconsin 53706²

Received 12 October 2007/ Accepted 26 October 2007

Sexual development in the human fungal pathogen Cryptococcus neoformans is a multistep process that results in the formation of spores, the likely infectious particles. A critical step in this developmental process is the transition from bud-form growth to filamentous growth. This transition is controlled by the homeodomain transcription factors Sxi1 and Sxi2a, whose targets are largely unknown. Here we describe the discovery of a gene, CLP1, that is regulated by Sxi1 and Sxi2a and is essential for sexual development. In vitro binding studies also show that the CLP1 promoter is bound directly by Sxi1 and Sxi2a. The deletion of CLP1 leads to a block in sexual development after cell fusion but before filament formation, and cells without CLP1 are unable to grow vegetatively after cell fusion. Our findings lead to a model in which CLP1 is a downstream target of the Sxi proteins that functions to promote growth after mating and to establish the filamentous state, a critical step in the production of spores.

Published ahead of print on 9 November 2007.

Present address: Department of Ophthalmology, University of Iowa, Carver College of Medicine, 375 Newton Road, 4111 Medical Education & Research Facility, Iowa City, IA 52242.