Abstract:
:The phenotype of the spontaneous mutant mouse hop-sterile (hop) is characterized by a hopping gait, polydactyly, hydrocephalus, and male sterility. Previous analyses of the hop mouse revealed a deficiency of inner dynein arms in motile cilia and a lack of sperm flagella, potentially accounting for the hydrocephalus and male sterility. The etiology of the other phenotypes and the location of the hop mutation remained unexplored. Here we show that the hop mutation is located in the Ttc26 gene and impairs Hedgehog (Hh) signaling. Expression analysis showed that this mutation led to dramatically reduced levels of the Ttc26 protein, and protein-protein interaction assays demonstrated that wild-type Ttc26 binds directly to the Ift46 subunit of Intraflagellar Transport (IFT) complex B. Although IFT is required for ciliogenesis, the Ttc26 defect did not result in a decrease in the number or length of primary cilia. Nevertheless, Hh signaling was reduced in the hop mouse, as revealed by impaired activation of Gli transcription factors in embryonic fibroblasts and abnormal patterning of the neural tube. Unlike the previously characterized mutations that affect IFT complex B, hop did not interfere with Hh-induced accumulation of Gli at the tip of the primary cilium, but rather with the subsequent dissociation of Gli from its negative regulator, Sufu. Our analysis of the hop mouse line provides novel insights into Hh signaling, demonstrating that Ttc26 is necessary for efficient coupling between the accumulation of Gli at the ciliary tip and its dissociation from Sufu.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Swiderski RE,Nakano Y,Mullins RF,Seo S,Bánfi Bdoi
10.1371/journal.pgen.1004689subject
Has Abstractpub_date
2014-10-23 00:00:00pages
e1004689issue
10eissn
1553-7390issn
1553-7404pii
PGENETICS-D-14-01181journal_volume
10pub_type
杂志文章相关文献
PLoS Genetics文献大全abstract::Genetic diversity across different human populations can enhance understanding of the genetic basis of disease. We calculated the genetic risk of 102 diseases in 1,043 unrelated individuals across 51 populations of the Human Genome Diversity Panel. We found that genetic risk for type 2 diabetes and pancreatic cancer d...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003447
更新日期:2013-05-01 00:00:00
abstract::Chemosensory pheromonal information regulates aggression and reproduction in many species, but how pheromonal signals are transduced to reliably produce behavior is not well understood. Here we demonstrate that the pheromonal signals detected by Gr32a-expressing chemosensory neurons to enhance male aggression are filt...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004356
更新日期:2014-05-22 00:00:00
abstract::Hypermutation of the immunoglobulin (Ig) genes requires Activation Induced cytidine Deaminase (AID) and transcription, but it remains unclear why other transcribed genes of B cells do not mutate. We describe a reporter transgene crippled by hypermutation when inserted into or near the Ig light chain (IgL) locus of the...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000332
更新日期:2009-01-01 00:00:00
abstract::Evolutionary forces that shape regulatory networks remain poorly understood. In mammals, the Rb pathway is a classic example of species-specific gene regulation, as a germline mutation in one Rb allele promotes retinoblastoma in humans, but not in mice. Here we show that p53 transactivates the Retinoblastoma-like 2 (R...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002731
更新日期:2012-06-01 00:00:00
abstract::Sleep is a nearly universal behavior that is regulated by diverse environmental stimuli and physiological states. A defining feature of sleep is a homeostatic rebound following deprivation, where animals compensate for lost sleep by increasing sleep duration and/or sleep depth. The fruit fly, Drosophila melanogaster, ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1008270
更新日期:2020-03-11 00:00:00
abstract::The female gametophyte of flowering plants, the embryo sac, develops within the diploid (sporophytic) tissue of the ovule. While embryo sac-expressed genes are known to be required at multiple stages of the fertilization process, the set of embryo sac-expressed genes has remained poorly defined. In particular, the set...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.0030171
更新日期:2007-10-01 00:00:00
abstract::Thermoanaerobic bacteria are of interest in cellulosic-biofuel production, due to their simultaneous pentose and hexose utilization (co-utilization) and thermophilic nature. In this study, we experimentally reconstructed the structure and dynamics of the first genome-wide carbon utilization network of thermoanaerobes....
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1002318
更新日期:2011-10-01 00:00:00
abstract::Epigenetic regulation of gene expression, including by Polycomb Group (PcG) proteins, may depend on heritable chromatin states, but how these states can be propagated through mitosis is unclear. Using immunofluorescence and biochemical fractionation, we find PcG proteins associated with mitotic chromosomes in Drosophi...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003135
更新日期:2012-01-01 00:00:00
abstract::Metabolic homeostasis in metazoans is regulated by endocrine control of insulin/IGF signaling (IIS) activity. Stress and inflammatory signaling pathways--such as Jun-N-terminal Kinase (JNK) signaling--repress IIS, curtailing anabolic processes to promote stress tolerance and extend lifespan. While this interaction con...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000460
更新日期:2009-04-01 00:00:00
abstract::Practical application of genomic-based risk stratification to clinical diagnosis is appealing yet performance varies widely depending on the disease and genomic risk score (GRS) method. Celiac disease (CD), a common immune-mediated illness, is strongly genetically determined and requires specific HLA haplotypes. HLA t...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004137
更新日期:2014-02-13 00:00:00
abstract::The evolution of metazoans from their choanoflagellate-like unicellular ancestor coincided with the acquisition of novel biological functions to support a multicellular lifestyle, and eventually, the unique cellular and physiological demands of differentiated cell types such as those forming the nervous, muscle and im...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003804
更新日期:2013-01-01 00:00:00
abstract::Sleep contributes to cognitive functioning and is sufficient to alter brain morphology and function. However, mechanisms underlying sleep regulation remain poorly understood. In mammals, tumor necrosis factor-alpha (TNFα) is known to regulate sleep, and cytokine expression may represent an evolutionarily ancient mecha...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007724
更新日期:2018-10-31 00:00:00
abstract::Generally, the second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiate...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006080
更新日期:2016-05-23 00:00:00
abstract::Viruses have exerted a constant and potent selective pressure on human genes throughout evolution. We utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants. Virus diversity (the number of different viruses in a geographic region) was used to measure virus-driv...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000849
更新日期:2010-02-19 00:00:00
abstract::MicroRNAs (miRNAs) are small, non-coding RNAs that play essential roles in plant growth, development, and stress response. We conducted a genome-wide survey of maize miRNA genes, characterizing their structure, expression, and evolution. Computational approaches based on homology and secondary structure modeling ident...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000716
更新日期:2009-11-01 00:00:00
abstract::Transposable elements are driving forces for establishing genetic innovations such as transcriptional regulatory networks in eukaryotic genomes. Here, we describe a silencer situated in the last 300 bp of the Mos1 transposase open reading frame (ORF) which functions in vertebrate and arthropod cells. Functional silenc...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005902
更新日期:2016-03-03 00:00:00
abstract::Inter-individual variation in gene regulatory elements is hypothesized to play a causative role in adverse drug reactions and reduced drug activity. However, relatively little is known about the location and function of drug-dependent elements. To uncover drug-associated elements in a genome-wide manner, we performed ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004648
更新日期:2014-10-02 00:00:00
abstract::Perennial questions of evolutionary biology can be applied to gene regulatory systems using the abundance of experimental data addressing gene regulation in a comparative context. What is the tempo (frequency, rate) and mode (way, mechanism) of transcriptional regulatory evolution? Here we synthesize the results of 23...
journal_title:PLoS genetics
pub_type: 杂志文章,评审
doi:10.1371/journal.pgen.1002432
更新日期:2012-01-01 00:00:00
abstract::Hypercholesterolemia is a causal and modifiable risk factor for atherosclerotic cardiovascular disease. A critical pathway regulating cholesterol homeostasis involves the receptor-mediated endocytosis of low-density lipoproteins into hepatocytes, mediated by the LDL receptor. We applied genome-scale CRISPR screening t...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1009285
更新日期:2021-01-29 00:00:00
abstract::Cyclophilin B (CyPB), encoded by PPIB, is an ER-resident peptidyl-prolyl cis-trans isomerase (PPIase) that functions independently and as a component of the collagen prolyl 3-hydroxylation complex. CyPB is proposed to be the major PPIase catalyzing the rate-limiting step in collagen folding. Mutations in PPIB cause re...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1004465
更新日期:2014-06-26 00:00:00
abstract::A form of dwarfism known as Meier-Gorlin syndrome (MGS) is caused by recessive mutations in one of six different genes (ORC1, ORC4, ORC6, CDC6, CDT1, and MCM5). These genes encode components of the pre-replication complex, which assembles at origins of replication prior to S phase. Also, variants in two additional rep...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1007041
更新日期:2017-10-16 00:00:00
abstract::Seed development in angiosperms is dependent on the interplay among different transcriptional programs operating in the embryo, the endosperm, and the maternally-derived seed coat. In angiosperms, the embryo and the endosperm are products of double fertilization during which the two pollen sperm cells fuse with the eg...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1001303
更新日期:2011-02-01 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pgen.1006788.]. ...
journal_title:PLoS genetics
pub_type: 已发布勘误
doi:10.1371/journal.pgen.1006893
更新日期:2017-07-12 00:00:00
abstract::Heteromorphic sex-determining regions or mating-type loci can contain large regions of non-recombining sequence where selection operates under different constraints than in freely recombining autosomal regions. Detailed studies of these non-recombining regions can provide insights into how genes are gained and lost, a...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1003724
更新日期:2013-08-01 00:00:00
abstract::Intestinal stem cell (ISC) self-renewal and proliferation are directed by Wnt/β-catenin signaling in mammals, whereas aberrant Wnt pathway activation in ISCs triggers the development of human colorectal carcinoma. Herein, we have utilized the Drosophila midgut, a powerful model for ISC regulation, to elucidate the mec...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005822
更新日期:2016-02-04 00:00:00
abstract::In the last two decades, mitochondrial DNA (mtDNA) and the non-recombining portion of the Y chromosome (NRY) have been extensively used in order to measure the maternally and paternally inherited genetic structure of human populations, and to infer sex-specific demography and history. Most studies converge towards the...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000200
更新日期:2008-09-26 00:00:00
abstract::Ocular coloboma results from abnormal embryonic development and is often associated with additional ocular and systemic features. Coloboma is a highly heterogeneous disorder with many cases remaining unexplained. Whole exome sequencing from two cousins affected with dominant coloboma with microcornea, cataracts, and s...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1005002
更新日期:2015-02-26 00:00:00
abstract::In the enterobacterial species Escherichia coli and Salmonella enterica, expression of horizontally acquired genes with a higher than average AT content is repressed by the nucleoid-associated protein H-NS. A classical example of an H-NS-repressed locus is the bgl (aryl-beta,D-glucoside) operon of E. coli. This locus ...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000405
更新日期:2009-03-01 00:00:00
abstract::Mutation of the DNA molecule is one of the most fundamental processes in biology. In this study, we use 283 parent-offspring trios to estimate the rate of mutation for both single nucleotide variants (SNVs) and short length variants (indels) in humans and examine the mutation process. We found 17812 SNVs, correspondin...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1006315
更新日期:2016-11-15 00:00:00
abstract::In Drosophila, dosage compensation augments X chromosome-linked transcription in males relative to females. This process is achieved by the Dosage Compensation Complex (DCC), which associates specifically with the male X chromosome. We previously found that the morphology of this chromosome is sensitive to the amounts...
journal_title:PLoS genetics
pub_type: 杂志文章
doi:10.1371/journal.pgen.1000066
更新日期:2008-05-02 00:00:00