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VEGETATIVE1 is essential for development of the compound inflorescence in pea
An understanding of the genetic network that controls the flower-bearing structure—the inflorescence—in plants helps to explain the diversity seen in plant forms. This work identifies a new mechanism for the generation of inflorescence complexity in legumes, which is based on the function of theVEG1gene.
- Ana Berbel
- , Cristina Ferrándiz
- & Francisco Madueño
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Article
| Open AccessDecreased extra-renal urate excretion is a common cause of hyperuricemia
Hyperuricemia, or gout, is thought to arise either from urate overproduction or from decreased renal excretion of urate. Ichidaet al. show that the extra-renal excretion of urate also has a role in the pathogenesis of hyperuricemia, and propose a new classification for patients with this disease.
- Kimiyoshi Ichida
- , Hirotaka Matsuo
- & Hiroshi Suzuki
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Transient activation of specific neurons in mice by selective expression of the capsaicin receptor
The ability to spatially and temporally control excitation of neuronsin vivo is an invaluable tool. By expressing the TRPV1 receptor in specific neuronal populations, Güler et al. have developed a rapid and noninvasive method to stimulate neuronal activity by the simple administration of capsaicin.
- Ali D. Güler
- , Aundrea Rainwater
- & Richard D. Palmiter
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RUNX1-induced silencing of non-muscle myosin heavy chain IIB contributes to megakaryocyte polyploidization
Megakaryocytes undergo polyploidization prior to forming platelets but this process is poorly characterised. In this study, non-muscle myosin IIB heavy chain, that localizes to the contractile ring during mitosis, is shown to be silenced prior to polyploidization in a RUNX1-dependent manner.
- Larissa Lordier
- , Dominique Bluteau
- & Yunhua Chang
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| Open AccessNew insights into the Tyrolean Iceman's origin and phenotype as inferred by whole-genome sequencing
The Tyrolean Iceman is 5,300 years old and his mitochondrial genome has been previously sequenced. This study reports the full genome sequence of the Iceman and reveals that he probably had brown eyes, was at risk for coronary disease and may have been infected with the pathogen Lyme borreliosis.
- Andreas Keller
- , Angela Graefen
- & Albert Zink
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miR-196b directly targets both HOXA9/MEIS1 oncogenes and FAS tumour suppressor in MLL-rearranged leukaemia
HOX9AandMEIS1are key oncogenes in MLL-rearranged leukaemia. miRNA-196b is shown here to directly suppress their expression and delay MLL-fusion-mediated leukaemia, but to also cause an aggressive leukaemia phenotype when expressed ectopically, suggesting that it targets tumour suppressors as well.
- Zejuan Li
- , Hao Huang
- & Jianjun Chen
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Humans and chimpanzees attend differently to goal-directed actions
Humans understand actions by making inferences about the person's intentions. Comparing humans with chimpanzees, this study shows that humans refer to the actors' faces more than chimpanzees do when observing goal-directed actions, indicating that humans view actions by integrating information from the actor.
- Masako Myowa-Yamakoshi
- , Céline Scola
- & Satoshi Hirata
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| Open AccessPPARγ contributes to PKM2 and HK2 expression in fatty liver
Molecular factors, regulating the expression of specific glycolytic enzymes that favour biosynthetic processes, have remained unknown. Panasyuket al. identify PPARγ as a novel transcription factor turning on pyruvate kinase M2 and hexokinase 2, which are frequently upregulated in pathophysiological growth.
- Ganna Panasyuk
- , Catherine Espeillac
- & Mario Pende
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| Open AccessDynamics of anterior–posterior axis formation in the developing mouse embryo
Detailed analysis of axis development in mouse embryo has been limited. Morriset al. developed an in vitroculture technique that enables the real-time observation of an anterior visceral endoderm formation and show that cell marker asymmetry within the AVE subdomain dictates the direction of the AVE migration.
- Samantha A. Morris
- , Seema Grewal
- & Magdalena Zernicka-Goetz
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Parkin controls dopamine utilization in human midbrain dopaminergic neurons derived from induced pluripotent stem cells
Mutations in parkin, an ubiquitin ligase, cause an inherited form of Parkinson's disease. Here, Jianget al. generate induced pluripotent stem cells from two patients with parkin mutations and find that neurons derived from the stem cells have defects in dopamine release, dopamine uptake and oxidative metabolism.
- Houbo Jiang
- , Yong Ren
- & Jian Feng
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Mouse and human strategies identify PTPN14 as a modifier of angiogenesis and hereditary haemorrhagic telangiectasia
Hereditary haemorrhagic telangiectasia (HTT) is caused by mutations in TGFβ/bone morphogenetic protein signalling genes. Here, Benzinouet al. show that variants of PTPN14, a gene within a mouse Tgfb1 modifier locus, associate with pulmonary arteriovenous malformation in HTT patients, shedding light on the molecular aetiology of this disease.
- Michael Benzinou
- , Frederic F. Clermont
- & Rosemary J. Akhurst
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| Open AccessAdvantage of rare infanticide strategies in an invasion experiment of behavioural polymorphism
The origin and maintenance of non-parental infanticide is a puzzling phenomenon in wild animal populations. This study of infanticide in a population of bank voles confirms negative frequency-dependent selection in nature and shows potential benefits of this apparently harmful behaviour.
- Tapio Mappes
- , Jouni Aspi
- & Juha Tuomi
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| Open AccessThe evolution of sensory divergence in the context of limited gene flow in the bumblebee bat
Populations of the same species living in different habitats can differ in sensory traits driving speciation, but it is not known if this variation limits gene flow. Here, a genetic and acoustic study of the bumblebee bat suggests that geographic distance, instead of echolocation divergence, limits gene flow.
- Sébastien J. Puechmaille
- , Meriadeg Ar Gouilh
- & Emma C. Teeling
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gp96 expression in neutrophils is critical for the onset of Escherichia coli K1 (RS218) meningitis
E. coliK1 can elude the innate immune system and cause neonatal meningitis. This study shows thatE. coli K1 enters polymorphonuclear leukocytes (PMNs) using gp96 to reduce the oxidative burst, and that PMN-depleted mice are resistant to E. coliK1 infection, suggesting that PMNs permit bacterial survival in the host.
- Rahul Mittal
- & Nemani V. Prasadarao
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Genetic dissection of axon regeneration via in vivo electroporation of adult mouse sensory neurons
Dorsal root ganglion neurons can regenerate after injury, but the mechanisms underlying axon regrowth are unclear. To address this, an electroporation transfection method is developed that can alter the gene expression of dorsal root ganglion cells in a living adult mouse, providing a tool to study axon regeneration.
- Saijilafu
- , Eun-Mi Hur
- & Feng-Quan Zhou
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MPP8 mediates the interactions between DNA methyltransferase Dnmt3a and H3K9 methyltransferase GLP/G9a
The methylation of DNA and histone H3 lysine 9 in chromatin are positively correlated. This study shows that the DNA methyl transferase Dnmt3a is methylated, and a crystal structure of Dnmt3a bound to the chromodomain protein MPP8 suggests a molecular mechanism.
- Yanqi Chang
- , Lidong Sun
- & Xiaodong Cheng
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miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells
The microRNA miR-137 is enriched in the brain of mice and induces the differentiation of adult neural stem cells. Now, Sun and colleagues report that miR-137 negatively regulates proliferation of neurons in embryonic mice and that TLX and LSD1 cooperate to negatively regulate miR-137 expression, blocking premature differentiation.
- GuoQiang Sun
- , Peng Ye
- & Yanhong Shi
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Large-scale DNA editing of retrotransposons accelerates mammalian genome evolution
APOBEC3 is a DNA editing enzyme that is important for antiviral responses. In this study, Carmi and colleagues show that APOBEC3 editing of retrotransposon sequences in mammalian genomes is widespread, with implications for the evolution of retrotransposons.
- Shai Carmi
- , George M. Church
- & Erez Y. Levanon
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| Open AccessSelective inhibition of microRNA accessibility by RBM38 is required for p53 activity
MicroRNAs bind to the 3′-untranslated region of genes to regulate expression. In this study, an RNA-binding protein, RMB38, is shown to selectively regulate the access of some microRNAs to their targets, and control the expression of some p53 target genes.
- Nicolas Léveillé
- , Ran Elkon
- & Reuven Agami
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| Open AccessTravelling and splitting of a wave of hedgehog expression involved in spider-head segmentation
During development, waves of gene expression are required for segmentation of the body axis. In this study, repeated splitting of a wave of hedgehog gene expression is shown during segmentation of the spiderAchaearanea tepidariorum.
- Masaki Kanayama
- , Yasuko Akiyama-Oda
- & Hiroki Oda
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| Open AccessGenome-wide association mapping reveals a rich genetic architecture of complex traits in Oryza sativa
Understanding the genetics and physiology of domesticated species is important for crop improvement. By studying natural variation and the phenotypic traits of 413 diverse accessions of rice, Zhao et al. identify many common genetic variants that influence quantitative traits such as seed size and flowering time.
- Keyan Zhao
- , Chih-Wei Tung
- & Susan R. McCouch
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| Open AccessA segmental genomic duplication generates a functional intron
The appearance of a new intron that splits an exon without disrupting the corresponding peptide sequence is a rare event in vertebrate genomes. Hellstenet al.demonstrate that, under certain circumstances, a functional intron can be produced in a single step by segmental genomic duplication.
- Uffe Hellsten
- , Julie L. Aspden
- & Daniel S. Rokhsar
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| Open AccessBlimp1 regulates the transition of neonatal to adult intestinal epithelium
Many mammals are born with an immature intestinal epithelium, which adapts to a changing diet during the weaning period. Muncanet al. show that the transcriptional repressor Blimp1is expressed in the intestine of mice at birth, and that expression is lost at the transition to the weaning stage.
- Vanesa Muncan
- , Jarom Heijmans
- & Gijs R. van den Brink
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| Open AccessA stem-group cnidarian described from the mid-Cambrian of China and its significance for cnidarian evolution
The origin of Cnidaria—coral and jellyfish—is still unsolved in the basal metazoan phylogeny. Here, a Cambrian fossil of a stem-group cnidarian,Cambroctoconus orientalisgen. et sp. nov., is found to bear octoradial symmetry, but no jelly-like mesenchyme, suggesting this evolved after octoradial symmetry.
- Tae-yoon Park
- , Jusun Woo
- & Duck K. Choi
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Discovery of lost diversity of paternal horse lineages using ancient DNA
Modern female horses are genetically diverse but male horses are relatively homogenous. Lippoldet al. sequence the Y chromosome of nine ancient horses and detect diversity in the ancestral paternal lineage, demonstrating ancient Y-chromosomal DNA sequencing can provide insights into evolution.
- Sebastian Lippold
- , Michael Knapp
- & Michael Hofreiter
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| Open AccessMesozoic retroposons reveal parrots as the closest living relatives of passerine birds
Zebra finches are passerine birds, but their phylogenetic relationship with non-passerine birds remains controversial. By examining retroposon insertion loci in avian genomes, the authors reveal that parrots are the closest relatives of passerines, which may have implications for understanding the evolution of birdsong.
- Alexander Suh
- , Martin Paus
- & Jürgen Schmitz
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Critical roles for EphB and ephrin-B bidirectional signalling in retinocollicular mapping
How retinoganglion cell axons project correctly to the superior colliculus is poorly understood. Here, projections are shown to require EphB1, EphB2 and ephrin-B1 to terminate in the medial superior colliculus, while ephrin-B2 is essential for the mapping of both dorsal and ventral axons.
- Sonal Thakar
- , George Chenaux
- & Mark Henkemeyer
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Insights into bird wing evolution and digit specification from polarizing region fate maps
Bird wings resemble the digits on the hands of dinosaurs, but which digit positions gave rise to those seen in modern birds is still unclear. In this work, long-term fate maps of the chick wing polarizing region are presented, supporting fossil data that birds descended from theropods that had digits 1, 2 and 3.
- Matthew Towers
- , Jason Signolet
- & Cheryll Tickle
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| Open AccessCytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni
The chronic disease schistosomiasis is caused by the blood flukeSchistosoma mansoni. By studying DNA modifications throughout the lifecycle of the pathogen, the authors identify DNA methylation as a factor in egg development and suggest that the epigenetic machinery responsible may be a therapeutic target.
- Kathrin K. Geyer
- , Carlos M. Rodríguez López
- & Karl F. Hoffmann
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Relative comparisons of call parameters enable auditory grouping in frogs
Male túngara frogs produce overlapping mating calls, which poses a challenge for the female frog to group and assign multiple auditory signals to the correct source. Farris and Ryan shows that, like humans, the female frogs compare and group signals using the smallest relative difference in call parameters.
- Hamilton E. Farris
- & Michael J. Ryan
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| Open AccessFunctional and molecular interactions between ERK and CHK2 in diffuse large B-cell lymphoma
Chk2 is a kinase that is a potential chemotherapeutic target. Here, Chk2 and the kinase ERK are shown to functionally interact, and are elevated in expression in human diffuse B-cell lymphomas. Combinatorial inhibition of the kinases was also shown to block tumour growth in anin vivomouse model.
- Bojie Dai
- , X. Frank Zhao
- & Ronald B. Gartenhaus
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The Wnt3a/β-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program
During development, Wnt-mediated Notch signalling controls the generation of somites from the presomitic mesoderm, but the precise signalling mechanism is unknown. Here, the transcription factor Mesogenin 1 is shown to be a direct target of Wnt3a and regulates the transcription of a Notch signalling program.
- Ravindra B. Chalamalasetty
- , William C. Dunty Jr
- & Terry P. Yamaguchi
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TorsinA participates in endoplasmic reticulum-associated degradation
The torsinA protein localizes to the endoplasmic reticulum and, when mutated, causes early onset torsion dystonia. The authors reveal a new role for torsinA in proteosome-mediated degradation of misfolded proteins, and relate this to endoplasmic reticulum stress, in aCaenorhabditis elegansmodel and patient fibroblasts.
- Flávia C. Nery
- , Ioanna A. Armata
- & Xandra O. Breakefield
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A photoconvertible fluorescent reporter to track chaperone-mediated autophagy
Soluble cytosolic proteins can be degraded in lysosomes by chaperone-mediated autophagy, however, the current method to measure this process requires isolation of lysosomes. Now, a fluorescent reporter is described that can measure this type of autophagy in intact cells.
- Hiroshi Koga
- , Marta Martinez-Vicente
- & Ana Maria Cuervo
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Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site
The sigma-2 receptor is used as a biomarker for tumour cell proliferation but its identity is unknown. Using a novel radiolabelled probe, the authors identify progesterone receptor membrane component 1, which is overexpressed in several tumour types, as the putative sigma-2 receptor.
- Jinbin Xu
- , Chenbo Zeng
- & Robert H. Mach
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Pyrimidine pool imbalance induced by BLM helicase deficiency contributes to genetic instability in Bloom syndrome
Mutations in the DNA helicaseBLM cause Bloom syndrome, which is characterized by slow replication fork progression and genetic instability. Here, cells lacking BLMare shown to have a defect in cytidine deaminase, which alters the pyrimidine pool and results in replication fork progression with altered velocity.
- Pauline Chabosseau
- , Géraldine Buhagiar-Labarchède
- & Mounira Amor-Guéret
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TRPV3 regulates nitric oxide synthase-independent nitric oxide synthesis in the skin
Nitric oxide can be produced by nitric oxide synthase or by nitrite reduction, but whether the latter occurs inside cells is unknown. Here, the TRPV3 ion channel is shown to induce nitrite-dependent nitric oxide production in keratinocytes, where it has a role in thermosensory behaviour and wound healing.
- Takashi Miyamoto
- , Matt J. Petrus
- & Ardem Patapoutian
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Cyclin B-dependent kinase 1 regulates human TRF1 to modulate the resolution of sister telomeres
TRF1 is a telomere binding protein involved in sister telomere cohesion. In this study, the ability of TRF1 to bind to telomeres in mitosis is inhibited by cyclin-dependent kinase 1-mediated phosphorylation, which may facilitate sister telomere resolution during mitosis.
- Megan McKerlie
- & Xu-Dong Zhu
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Convergent evolution in locomotory patterns of flying and swimming animals
Undulating flight, an efficient mode of locomotion in flying birds, can theoretically also result in efficient locomotion in water. Here we demonstrate gait patterns resembling undulating flight in four marine vertebrate species comprising sharks and pinnipeds.
- Adrian C. Gleiss
- , Salvador J. Jorgensen
- & Rory P. Wilson
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Article
| Open AccessNeural coding in a single sensory neuron controlling opposite seeking behaviours in Caenorhabditis elegans
The neuronal mechanisms responsible for thermal seeking behaviour inCaenorhabditis. elegansare not fully understood. In this study, the sensory neuron AFD is shown to be involved in the responses to both cold and warm temperatures by transmitting inhibitory and excitatory signals to the interneuron AIY.
- Atsushi Kuhara
- , Noriyuki Ohnishi
- & Ikue Mori
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Contemporary and historical separation of transequatorial migration between genetically distinct seabird populations
Migratory segregation presents a hypothesized barrier to gene flow among seabirds, but its mechanisms are unclear. Rayneret al. find that migratory habitat specialization, associated with breeding asynchrony and philopatry, restricts gene flow between two seabird populations migrating across the Pacific Ocean.
- Matt J. Rayner
- , Mark E. Hauber
- & Scott A. Shaffer
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Article
| Open AccessGenetics and the environment converge to dysregulate N-glycosylation in multiple sclerosis
Complex diseases such as multiple sclerosis have both genetic and environmental components. This study demonstrates that variants of genes implicated in multiple sclerosis, and alterations in cellular metabolism and vitamin D3 levels, alterN-glycosylation, a post-translational modification causal of the disease in mice.
- Haik Mkhikian
- , Ani Grigorian
- & Michael Demetriou
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An evolutionarily conserved three-dimensional structure in the vertebrate Irx clusters facilitates enhancer sharing and coregulation
TheIrx genes are arranged in clusters and the reason for this arrangement is unclear. Using a chromatin conformation capture assay, the authors show that Irx genes share enhancer elements, suggesting that the gene cluster is required for coregulation of the Irxgenes.
- Juan J. Tena
- , M. Eva Alonso
- & José Luis Gómez-Skarmeta
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α-Mannosidase 2C1 attenuates PTEN function in prostate cancer cells
PTEN is a phosphatase that regulates the phosphatidylinositol-3 kinase signalling pathway and is inactivated in many tumour types. Heet al.show that a mannosidase, α-mannosidase 2C1, can inactivate PTEN in prostate cancer cells, and that PTEN-positive human prostate tumours overexpress α-mannosidase 2C1.
- Lizhi He
- , Catherine Fan
- & Damu Tang
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Article
| Open AccessRespiratory distress and perinatal lethality in Nedd4-2-deficient mice
In vitrostudies have suggested that the ubiquitin ligase, Nedd4-2, regulates several proteins, including the epithelial sodium channel. Here by examining Nedd4-2-deficient mice, the authors demonstrate that Nedd4-2 is essential for epithelial sodium channel regulation, fetal and postnatal lung function and animal survival.
- Natasha A. Boase
- , Grigori Y. Rychkov
- & Sharad Kumar
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Article
| Open AccessConvergent evolution in biosynthesis of cyanogenic defence compounds in plants and insects
Cyanide-releasing defence systems in plants and animals are important to the evolution of plant–herbivore interactions. The authors identify the enzymes responsible for biosynthesis of cyanogenic glucosides by Six-spot Burnet moth caterpillars, which have evolved independently from the known plant pathway.
- Niels Bjerg Jensen
- , Mika Zagrobelny
- & Søren Bak
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Article
| Open AccessThe global distribution of the Duffy blood group
The global prevalence of the Duffy blood group variants is important due to the resistance that the Duffy-negative phenotype generally confers uponPlasmodium vivax infection. Hay et al.generate global frequency maps of the common Duffy alleles to show transmission patterns of the malaria parasite.
- Rosalind E. Howes
- , Anand P. Patil
- & Simon I. Hay
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Article
| Open AccessIntestinal epithelial stem cells do not protect their genome by asymmetric chromosome segregation
It has been proposed that stem cells use nonrandom chromosome segregation to avoid the accumulation of replication-induced mutations. Here, the authors examine intestinal epithelial stem cell division and show, using label exclusion and retention assays, that the cells segregate their chromosomes randomly.
- Marion Escobar
- , Pierre Nicolas
- & Catherine Legraverend
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Wwp2 is essential for palatogenesis mediated by the interaction between Sox9 and mediator subunit 25
Sox9 is an important transcription factor in the formation of cartilage chondrogenesis that occurs during skeletal development. Nakamuraet al.show that Sox9 interacts with Wwp2 and Med25 to form a complex and that loss of either protein in zebrafish results in altered palate chondrogenesis.
- Yukio Nakamura
- , Koji Yamamoto
- & Haruhiko Akiyama
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