Genetic circuits that govern bisexual and unisexual reproduction in Cryptococcus neoformans.
Genetic circuits that govern bisexual and unisexual reproduction in Cryptococcus neoformans.
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DOI：
10.1371/journal.pgen.1003688
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Heitman J
中科院分区：
文献类型：
--
作者：
Feretzaki M;Heitman J
新型隐球菌是一种具有明确性周期的人类真菌病原体。营养限制条件和信息素诱导从单细胞酵母到多细胞菌丝的二态转变和感染性孢子的产生。有性生殖涉及细胞的对生（两性）或一个（单性）交配类型。两性和单性生殖是由保守的信息素敏感Cpk 1 MAPK信号转导级联的共享组件，并通过Mat 2，该途径的主要转录调节。然而，该途径的下游靶标在很大程度上是未知的，并且基于同源性的方法未能产生下游转录调节因子或其他靶标。在这项研究中，我们应用插入诱变通过根癌农杆菌transkingdom DNA传递，以确定具有单性生殖缺陷的突变体。除了已知参与性发育的元素（Crg 1，Ste 7，Mat 2和Znf 2）外，我们的筛选还确定了性发育的三个关键调节因子：Znf 3，Spo 11和Ubc 5。Spo 11和Ubc 5在两性和单性生殖过程中都促进孢子形成。遗传和表型分析提供了进一步的证据，暗示这两个基因在减数分裂的调节。性发育的表型分析表明，Znf 3是所需的单性生殖过程中的菌丝发育，也发挥了重要作用，在两性生殖。Znf 3通过与信息素信号级联反应平行且独立的途径促进细胞融合和信息素产生。令人惊讶的是，Znf 3在单性生殖过程中参与转座子沉默，并可能作为RNAi沉默和性发育之间的联系。我们的研究说明了无偏见的遗传筛选的力量，以揭示新的和保守的电路，操作有性生殖。有性生殖驱动着整个真核生物王国的遗传多样性，也清除了有害的突变。性发育通常发生在异性或交配型的伴侣之间;然而，在缺乏相容伴侣的情况下，在某些真菌物种中可以发生单性生殖，仅涉及一种交配型的细胞。人类病原真菌新生隐球菌在两性和单性生殖过程中经历了二态转换。遗传回路如何控制和区分这些发展级联是未知的。我们采用了全基因组插入突变的方法结合转录谱，以确定三个新的因素，影响不同阶段的菌丝发育过程中的两性和单性生殖。Znf 3在有性生殖过程中协调菌丝发育，Spo 11和Ubc 5是生产可行的减数分裂孢子后代所必需的。本文的研究结果说明了控制两种不同有性生殖模式的遗传电路的复杂性，并为进一步阐明分子途径之间的沟通和相互作用提供了基础。
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. Sexual reproduction drives genetic diversity throughout the eukaryotic kingdom and also purges deleterious mutations. Sexual development usually occurs between partners of opposite sex or mating type; however, in the absence of a compatible partner, unisexual reproduction can occur involving cells of only one mating type in some fungal species. The human fungal pathogen Cryptococcus neoformans undergoes a dimorphic switch during bisexual and unisexual reproduction. How genetic circuits control and distinguish these developmental cascades was unknown. We employed a genome-wide insertional mutagenesis approach combined with transcriptional profiling to identify three novel factors that affect different stages of hyphal development during bisexual and unisexual reproduction. Znf3 orchestrates hyphal development during sexual reproduction, and Spo11 and Ubc5 are required for the production of viable meiotic spore progeny. The findings presented here illustrate the complexity of genetic circuits that govern the two distinct modes of sexual reproduction and offer a foundation to further elucidate the communication and interaction between the molecular pathways.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
56.9
作者：
Alonso, JM;Stepanova, AN;Ecker, JR
通讯作者：
Ecker, JR
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
3.6
作者：
Davidson, RC;Nicholls, CB;Heitman, J
通讯作者：
Heitman, J
影响因子：
3
作者：
Davidson, RC;Cruz, MC;Heitman, J
通讯作者：
Heitman, J