Cell identity and sexual development in Cryptococcus neoformans are controlled by the mating-type-specific homeodomain protein Sxi1α
Open accessAbstract
Virulence in the human fungal pathogen Cryptococcus neoformans is associated with the α mating type. Studies to identify the properties of α 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 MATα components are insufficient to regulate sexual differentiation, and we identify a novel α-specific regulator,SXI1α. Our data show that SXI1α establishes α cell identity and controls progression through the sexual cycle, and we discover that ectopic expression of SXI1α in a cells is sufficient to drive a/α sexual development. SXI1α 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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The mating type specific homeodomain protein Sxi1α of C. neoformans is important for events after cell fusion.
“The mating type specific homeodomain protein Sxi1α of C. neoformans is important for events after cell fusion [27].”
From Light Controls Growth and Development via a Conserved Pathway in the Fungal Kingdom (2005) · cites this paper as [27]
The SXI1α gene encodes the MATα-specific homeodomain protein.
“The SXI1α gene, which encodes the MATα-specific homeodomain protein [27], was introduced into the genome of a MATa haploid strain.”
From Light Controls Growth and Development via a Conserved Pathway in the Fungal Kingdom (2005) · cites this paper as [27]
Overexpression of a mating type-specific homeodomain protein in a haploid strain of the opposite mating type confers a self-filamentous morphology.
“However, overexpression of a mating type-specific homeodomain protein in a haploid strain of the opposite mating type confers a self-filamentous morphology [27].”
From Light Controls Growth and Development via a Conserved Pathway in the Fungal Kingdom (2005) · cites this paper as [27]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
Altschul, S. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.17.3389 · Cited by 73,302 · see citing works
Church, G. M., & Gilbert, W. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.7.1991 · Cited by 8,213 · see citing works
Site-directed mutagenesis by overlap extension using the polymerase chain reaction
Ho, S. N., Hunt, H. D., Horton, R. M., Pullen, J. K., & Pease, L. R. (1989) · Gene · doi:10.1016/0378-1119(89)90358-2 · Cited by 7,354 · see citing works
Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension
Horton, R. M., Hunt, H. D., Ho, S. N., Pullen, J. K., & Pease, L. R. (1989) · Gene · doi:10.1016/0378-1119(89)90359-4 · Cited by 3,020 · see citing works
Guide to Yeast Genetics and Molecular Biology
Kurtzman, C. P., Guthrie, C., & Fink, G. R. (1993) · Mycologia · doi:10.2307/3760517 · Cited by 2,363 · see citing works
Signal Transduction Cascades Regulating Fungal Development and Virulence
Lengeler, K. B., Davidson, R. C., D'souza, C., Harashima, T., Shen, W.-C., Wang, P., Pan, X., Waugh, M., & Heitman, J. (2000) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.64.4.746-785.2000 · Cited by 915 · see citing works
Self-citationCasadevall, A., & Perfect, J. R. (1998) · ASM Press eBooks · doi:10.1128/9781555818241 · Cited by 673 · see citing works
Bürglin, T. R. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.21.4173 · Cited by 615 · see citing works
Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA
Toffaletti, D. L., Rude, T. H., Johnston, S. A., Durack, D. T., & Perfect, J. R. (1993) · Journal of Bacteriology · doi:10.1128/jb.175.5.1405-1411.1993 · Cited by 488 · see citing works
Genetic association of mating types and virulence in Cryptococcus neoformans
Kwon-Chung, K. J., Edman, J. C., & Wickes, B. L. (1992) · Infection and Immunity · doi:10.1128/iai.60.2.602-605.1992 · Cited by 437 · see citing works
Mating types and sexual development in filamentous ascomycetes
Coppin, E., Debuchy, R., Arnaise, S., & Picard-Bennoun, M. (1997) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.61.4.411-428.1997 · Cited by 424 · see citing works
Cryptococcus neoformans mating and virulence are regulated by the G-protein α subunit GPA1 and cAMPPreprint
Alspaugh, J. A., Perfect, J. R., & Heitman, J. (1997) · Genes & Development · doi:10.1101/gad.11.23.3206 · Cited by 403 · see citing works
Self-citationBanuett, F., & Herskowitz, I. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.15.5878 · Cited by 398 · see citing works
Hartwell, L. H. (1980) · The Journal of Cell Biology · doi:10.1083/jcb.85.3.811 · Cited by 364 · see citing works
Identification of a Mating Type-Like Locus in the Asexual Pathogenic Yeast Candida albicans
Hull, C. M., & Johnson, A. D. (1999) · Science · doi:10.1126/science.285.5431.1271 · Cited by 363 · see citing works
Self-citationMolecular Genetics of Mating Recognition in Basidiomycete Fungi
Casselton, L. A., & Olesnicky, N. S. (1998) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.62.1.55-70.1998 · Cited by 353 · see citing works
Dimorphism and haploid fruiting in Cryptococcus neoformans: association with the alpha-mating type.
Wickes, B. L., Mayorga, M. E., Edman, U., & Edman, J. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.14.7327 · Cited by 307 · see citing works
MATING TYPE IN FILAMENTOUS FUNGI
Kronstad, J. W., & Staben, C. (1997) · Annual Review of Genetics · doi:10.1146/annurev.genet.31.1.245 · Cited by 298 · see citing works
A PCR-based strategy to generate integrative targeting alleles with large regions of homology
Davidson, R. C., Blankenship, J. R., Kraus, P. R., de Jesús-Berrı́os, M., Hull, C. M., D’Souza, C. A., Wang, P., & Heitman, J. (2002) · Microbiology · doi:10.1099/00221287-148-8-2607 · Cited by 296 · see citing works
Self-citationIdentification of genes in the bW/bE regulatory cascade in Ustilago maydis
Brachmann, A., Weinzierl, G., Kämper, J., & Kahmann, R. (2001) · Molecular Microbiology · doi:10.1046/j.1365-2958.2001.02699.x · Cited by 292 · see citing works
Kämper, J., Reichmann, M., Romeis, T., Bölker, M., & Kahmann, R. (1995) · Cell · doi:10.1016/0092-8674(95)90372-0 · Cited by 270 · see citing works
Mating-Type Locus of Cryptococcus neoformans : a Step in the Evolution of Sex Chromosomes
Lengeler, K. B., Fox, D. S., Fraser, J. A., Allen, A., Forrester, K., Dietrich, F. S., & Heitman, J. (2002) · Eukaryotic Cell · doi:10.1128/ec.1.5.704-718.2002 · Cited by 266 · see citing works
Self-citationPitkin, J. W., Panaccione, D. G., & Walton, J. D. (1996) · Microbiology · doi:10.1099/13500872-142-6-1557 · Cited by 264 · see citing works
APPLICATION OF MATING TYPE GENE TECHNOLOGY TO PROBLEMS IN FUNGAL BIOLOGY
Turgeon, B. G. (1998) · Annual Review of Phytopathology · doi:10.1146/annurev.phyto.36.1.115 · Cited by 262 · see citing works
Crystal Structure of the MATa1/MATα2 Homeodomain Heterodimer Bound to DNA
Li, T., Stark, M. R., Johnson, A. D., & Wolberger, C. (1995) · Science · doi:10.1126/science.270.5234.262 · Cited by 256 · see citing works
Molecular mechanisms of cell-type determination in budding yeast
Johnson, A. D. (1995) · Current Opinion in Genetics & Development · doi:10.1016/0959-437x(95)80022-0 · Cited by 189 · see citing works
Electron Microscopy of the Arthus Reaction, Using Ferritin as Antigen
SABESIN, S. M., & BANFIELD, W. G. (1961) · Experimental Biology and Medicine · doi:10.3181/00379727-107-26683 · Cited by 178 · see citing works
The α-Mating Type Locus of Cryptococcus neoformans Contains a Peptide Pheromone Gene
Moore, T. D. E., & Edman, J. C. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.3.1962-1970.1993 · Cited by 170 · see citing works
Cryptococcus neoformans STE12α Regulates Virulence but Is Not Essential for Mating
Chang, Y. C., Wickes, B. L., Miller, G., Penoyer, L. A., & Kwon-Chung, K. J. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.5.871 · Cited by 143 · see citing works
SEX IN THE 90s:SRYand the Switch to the Male Pathway
Capel, B. (1998) · Annual Review of Physiology · doi:10.1146/annurev.physiol.60.1.497 · Cited by 138 · see citing works
Yue, C., Cavallo, L. M., Alspaugh, J. A., Wang, P., Cox, G. M., Perfect, J. R., & Heitman, J. (1999) · Genetics · doi:10.1093/genetics/153.4.1601 · Cited by 130 · see citing works
Self-citationSex Determination and Dosage Compensation: Lessons from Flies and Worms
Parkhurst, S. M., & Meneely, P. (1994) · Science · doi:10.1126/science.8178152 · Cited by 129 · see citing works
Diploid Strains of the Pathogenic Basidiomycete Cryptococcus neoformans Are Thermally Dimorphic
Sia, R. A. L., Lengeler, K. B., & Heitman, J. (2000) · Fungal Genetics and Biology · doi:10.1006/fgbi.2000.1192 · Cited by 118 · see citing works
Self-citationRegulation of Sexual Dimorphism in Mammals
Haqq, C. M., & Donahoe, P. K. (1998) · Physiological Reviews · doi:10.1152/physrev.1998.78.1.1 · Cited by 110 · see citing works
Characterization of the MFα pheromone of the human fungal pathogen Cryptococcus neoformans
Davidson, R. C., Moore, T. D. E., John, A. R. O., & Heitman, J. (2000) · Molecular Microbiology · doi:10.1046/j.1365-2958.2000.02213.x · Cited by 67 · see citing works
Self-citationZhao, H., Lu, M., Singh, R., et al. (2001) · Genes & Development · doi:10.1101/gad.919501 · Cited by 66 · see citing works
Morphogenesis of Cryptococcus neoformans
Alspaugh, J. A., Davidson, R. C., & Heitman, J. (2000) · KARGER eBooks · doi:10.1159/000060352 · Cited by 63 · see citing works
Self-citationClarke, D. L., Woodlee, G. L., McClelland, C. M., Seymour, T. S., & Wickes, B. L. (2001) · Molecular Microbiology · doi:10.1046/j.1365-2958.2001.02375.x · Cited by 63 · see citing works
Karos, M., Chang, Y. C., McClelland, C. M., Clarke, D. L., Fu, J., Wickes, B. L., & Kwon-Chung, K. J. (2000) · Journal of Bacteriology · doi:10.1128/jb.182.21.6222-6227.2000 · Cited by 54 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- Ausubel, F.M., Brent, R., Kingston, R.E., Moore, D.D., Seidman, J.G., Smith, J.A., and Struhl, K., eds. 1992. Current protocols in molecular biology. Greene Publishing Associates and Wiley-Interscience, New York.
- Casadevall, C. and Perfect, J.R. 1998. Cryptococcus neofor- mans, 1st ed. ASM Press, Washington, DC.
- Herskowitz, I., Rine, J., and Strathern, J. 1992. Mating-type de- termination and mating-type interconversion in Saccharo- myces cerevisiae. In Molecular and cellular biology of the yeast Saccharomyces: Gene Expression (eds. E.W. Jones et al.), pp. 583-656. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
Cited by
Sorted by citations
Cryptococcal cell morphology affects host cell interactions and pathogenicity
Okagaki, L. H., Strain, A. K., Nielsen, J. N., Charlier, C., Baltes, N. J., Chrétien, F., Heitman, J., Dromer, F., & Nielsen, K. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000953 · Cited by 345 · see citing works
Self-citationLight Controls Growth and Development via a Conserved Pathway in the Fungal Kingdom
Idnurm, A., & Heitman, J. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030095 · Cited by 310 · see citing works
Self-citationBahn, Y.-S., Cox, G. M., Perfect, J. R., & Heitman, J. (2005) · Current Biology · doi:10.1016/j.cub.2005.09.047 · Cited by 205 · see citing works
Self-citationChun, C. D., Liu, O. W., & Madhani, H. D. (2007) · PLoS Pathogens · doi:10.1371/journal.ppat.0030022 · Cited by 181 · see citing works
Bennett, R. J., Forche, A., & Berman, J. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019604 · Cited by 118 · see citing works
Okagaki, L. H., Wang, Y., Ballou, E. R., O'Meara, T. R., Bahn, Y.-S., Alspaugh, J. A., Xue, C., & Nielsen, K. (2011) · Eukaryotic Cell · doi:10.1128/ec.05179-11 · Cited by 117 · see citing works
- Authors
- Hull, C. M., Davidson, R. C., & Heitman, J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2002-12-01
- Volume
- 16
- Issue
- 23
- Pages
- 3046-3060
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC187491
- OpenAlex
- W2108365583
- Cited by
- 119
- References
- 39
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 1 · 2019: 6 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 16 · 2013: 6 · 2012: 5
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Damon Runyon Cancer Research Foundation
- Wellcome Trust
- National Institutes of Health (2r01ai050113-16a1, 5u01ai047087-03, 5u01ai048594-02)
- National Institute of Allergy and Infectious Diseases (U01 AI48594, R01 AI50113, AI50113, P01AI044975, U01AI47087, R01-AI050113, AI-44975)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Cryptococcus neoformans, homeodomain transcription factor, mating type, sexual differentiation, cell identity, cell fate, fungal pathogenesis, virulence
- MeSH terms
- Cryptococcus neoformans, Diploidy, Fungal Proteins, Genes, Fungal, Molecular Sequence Data, Homeodomain Proteins, Hyphae, Genes, Mating Type, Fungal
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
