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Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus
The genes encoding cryptochromes are implicated in regulating circadian rhythms in mammals. Ono and colleagues monitor circadian rhythms in cultured suprachiasmatic nucleus tissue from transgenic mice lacking cryptochromes, and find that circadian rhythms are present in neonates but not mature animals.
- Daisuke Ono
- , Sato Honma
- & Ken-ichi Honma
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Ets2-dependent trophoblast signalling is required for gastrulation progression after primitive streak initiation
The transcription factor Ets2 is expressed in the extraembryonic ectoderm tropoblast during gastrulation. Here, the authors use Ets2 knock-out mice to show that Ets2 signalling is required for gastrulation, primitive streak elongation and development and the mesoderm epithelial-to-mesenchymal transition.
- Christiana Polydorou
- & Pantelis Georgiades
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| Open AccessTrunk exoskeleton in teleosts is mesodermal in origin
Trunk exoskeleton elements of non-tetrapods such as scales and fin rays are believed to derive from the neural crest. Shimada and colleagues use long-term cell labelling methods to show that these elements are actually derived from the mesoderm.
- Atsuko Shimada
- , Toru Kawanishi
- & Hiroyuki Takeda
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| Open AccessRnd3 coordinates early steps of cortical neurogenesis through actin-dependent and -independent mechanisms
The atypical RhoGTPase Rnd3 is implicated in the regulation of neuronal migration in the embryonic cerebral cortex. Using gene silencing techniques, Pacary and colleagues find that Rnd3 is also involved in earlier stages of neurogenesis, by modulating actin filament polymerization and cyclin D1 translation.
- Emilie Pacary
- , Roberta Azzarelli
- & François Guillemot
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Impaired endolysosomal function disrupts Notch signalling in optic nerve astrocytes
Crystallins are structural proteins that are expressed on the outside of the lens of the eye. Valapala and colleagues find that specific crystallins in retinal astrocytes regulate V-ATPase activity and endolysosomal acidification, to facilitate optimal Notch signalling during retinal development.
- Mallika Valapala
- , Stacey Hose
- & Debasish Sinha
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| Open AccessThe transcriptional repressor NKAP is required for the development of iNKT cells
The transcriptional repressor NKAP is required at an early stage of T cell development for the differentiation of αβ T cells. Thapa et al.now show that at a later stage, NKAP has a specific role in positive selection of double positive thymocytes into the iNKT cell lineage.
- Puspa Thapa
- , Joy Das
- & Virginia Smith Shapiro
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MacroH2A histone variants act as a barrier upon reprogramming towards pluripotency
Chromatin templates can act as barriers against cellular reprogramming. Gaspar-Maia and colleagues use mouse models deficient in the histone variants macroH2A1 and macroH2A2, and find that macroH2A functions as an epigenetic barrier against induced pluripotency by silencing Utx target genes.
- Alexandre Gaspar-Maia
- , Zulekha A. Qadeer
- & Emily Bernstein
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Haemogenic endocardium contributes to transient definitive haematopoiesis
Cardiac and endocardial/endothelial cells arise from progenitor cells expressing multiple haematopoietic transcription factors. Nakano and colleagues find that Nkx2–5-positive endocardial cells serve as a de novosource for definitive haematopoietic progenitors during mammalian embryogenesis.
- Haruko Nakano
- , Xiaoqian Liu
- & Atsushi Nakano
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| Open AccessXenoturbella bocki exhibits direct development with similarities to Acoelomorpha
Xenoturbella is a simple marine worm recently suggested to be either a deuterostome or an early branching bilaterian. Nakano et al. report the first observations of naturally spawned eggs and embryos from Xenoturbella, and uncover new insights into the evolutionary history of metazoan development.
- Hiroaki Nakano
- , Kennet Lundin
- & Michael C. Thorndyke
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Interactions between Twist and other core epithelial–mesenchymal transition factors are controlled by GSK3-mediated phosphorylation
Twist is an epithelial–mesenchymal transition regulatory factor that is implicated in neural crest development and cancer. Lander and colleagues show that Twist interacts with Snail proteins to inhibit their function, and that this interaction is regulated by phosphorylation of the Twist C terminus.
- Rachel Lander
- , Talia Nasr
- & Carole LaBonne
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| Open AccessIGF-1 promotes the development and cytotoxic activity of human NK cells
Insulin-like growth factor (IGF)-1 regulates many physiological functions including growth and metabolism. Ni et al.show that human natural killer cells secrete IGF-1 and that IGF-1 enhances the development and cytotoxicity of these cells.
- Fang Ni
- , Rui Sun
- & Haiming Wei
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Developmental evidence for serial homology of the vertebrate jaw and gill arch skeleton
It is generally believed that jaws evolved from a gill arch, but this is unsupported by palaeontological or developmental data. Gillis et al. study three gnathostome taxa and identify a conserved molecular mechanism that delineates the dorsal and ventral skeletal segments of the jaw, hyoid and gill arches.
- J. Andrew Gillis
- , Melinda S. Modrell
- & Clare V. H. Baker
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| Open AccessGenome of the Chinese tree shrew
The Chinese tree shrew, Tupaia belangeri chinensis, has been proposed as a potential animal model in biomedical research and drug safety testing. This study presents the full genome of the Chinese tree shrew, identifying common features between the tree shrew and primates.
- Yu Fan
- , Zhi-Yong Huang
- & Yong-Gang Yao
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| Open AccessHuman CLPP reverts the longevity phenotype of a fungal ClpP deletion strain
The mitochondrial protease CLPP is found in most eukaryotic organisms but its biological role has been unclear. Here Osiewacz and colleagues show that deletion of CLPP extends lifespan of the filamentous fungus Podospora anserina, and that human and fungal CLPP are functionally conserved.
- Fabian Fischer
- , Andrea Weil
- & Heinz D. Osiewacz
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The phosphatase Dullard negatively regulates BMP signalling and is essential for nephron maintenance after birth
Kidney maintenance and function are essential for a healthy organism. Here Nishinakamura and colleagues show that the phosphatase Dullard suppresses BMP signalling and apoptosis in the mouse kidney and that Dullard is required for the maintenance of functional nephrons after birth.
- Masaji Sakaguchi
- , Sazia Sharmin
- & Ryuichi Nishinakamura
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Analysis of protein-coding mutations in hiPSCs and their possible role during somatic cell reprogramming
Recent studies have shown that human induced pluripotent stem cells contain point mutations in coding regions, but the functional significance of these mutations is unclear. Here the authors provide evidence that these mutations are unlikely to confer a selective advantage for reprogramming.
- Sergio Ruiz
- , Athurva Gore
- & Juan Carlos Izpisua Belmonte
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| Open AccessRab9 and retromer regulate retrograde trafficking of luminal protein required for epithelial tube length control
The development of biological tubes is regulated by mutual interactions between cells and luminal extracellular matrix. Donget al. show that retrograde recycling of luminal chitin deacetylase regulates Drosophila tracheal tubule geometry by restricting length independently of diameter.
- Bo Dong
- , Ken Kakihara
- & Shigeo Hayashi
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Splicing factor SRSF3 is crucial for hepatocyte differentiation and metabolic function
Splicing factors, such as the protein SRSF3, regulate mRNA metabolism but are hard to study in vivobecause genetic kockouts are usually lethal. Here, Sen and colleagues create mice with a hepatocyte-specific knockout of Srsf3 and demonstrate its role in hepatocyte differentiation and liver function.
- Supriya Sen
- , Hassan Jumaa
- & Nicholas J. G. Webster
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Fluid flow and interlinked feedback loops establish left–right asymmetric decay of Cerl2 mRNA
During embryonic development, midline fluid flow results in asymmetric nodal gene expression. Using genetic manipulations and mathematical modelling, Nakamura et al. find that expression of the nodal antagonist Cerl2 is regulated post-transcriptionally, and that asymmetry is maintained by Wnt-Cerl2 feedback loops.
- Tetsuya Nakamura
- , Daisuke Saito
- & Hiroshi Hamada
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| Open AccessPioneer glutamatergic cells develop into a morpho-functionally distinct population in the juvenile CA3 hippocampus
The heterogeneity of cortical interneurons results from spatio-temporal differences in embryonic origin. Marissal et al. show that early-generated glutamatergic neurons display distinct morpho-functional features, suggesting that temporal factors are also important in determining glutamatergic function.
- Thomas Marissal
- , Paolo Bonifazi
- & Rosa Cossart
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DJ-1 promotes angiogenesis and osteogenesis by activating FGF receptor-1 signaling
Osteoblasts and endothelial cells have important roles in bone regeneration. Kim and colleagues identify the protein DJ-1 as an angiogenic and osteogenic signalling molecule involved in the cross-talk between these cells and show that DJ-1 promotes bone regeneration and fracture healing in mice.
- Jung-Min Kim
- , Hong-In Shin
- & Pann-Ghill Suh
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The developmental basis of bat wing muscle
Phylogenetic bat studies suggest that powered flight is evolutionarily conserved. Tokita et al.find that bat wing muscles are derived from multiple myogenic sources with different embryonic origins, and that spatiotemporal correlations exist between outgrowth of wing membranes and expansion of wing muscles.
- Masayoshi Tokita
- , Takaaki Abe
- & Kazuo Suzuki
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Preotic neural crest cells contribute to coronary artery smooth muscle involving endothelin signalling
Endothelin-1 regulates cardiovascular development by acting on neural crest cells. Here endothelin-1-deficient mice are studied, revealing that preotic neural crest cells differentiate into coronary artery smooth muscle cells through endothelin-1-dependent mechanisms.
- Yuichiro Arima
- , Sachiko Miyagawa-Tomita
- & Hiroki Kurihara
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Reprogramming to pluripotency is an ancient trait of vertebrate Oct4 and Pou2 proteins
The mammalian transcription factors Oct4 and Pou2 are implicated in germ cell pluripotency induction and maintenance. Tapia and colleagues find that axolotl Pou2 and Oct4 reprogram mouse and human fibroblasts to a pluripotent state, suggesting ancestral Oct4 and Pou2 gene function is evolutionarily conserved.
- Natalia Tapia
- , Peter Reinhardt
- & Hans R. Schöler
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| Open AccessDynamic blastomere behaviour reflects human embryo ploidy by the four-cell stage
Abnormal human embryo development is implicated in the embryo arrest observed during in vitrofertilization. Chavez and colleagues perform time-lapse imaging on human embryos and find that chromosomally abnormal embryos exhibit diverse cell cycle parameters that may contribute to arrest.
- Shawn L. Chavez
- , Kevin E. Loewke
- & Renee A. Reijo Pera
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| Open AccessThe Hedgehog signalling pathway regulates autophagy
Autophagy is a cellular process that controls protein and organelle turnover. Jimenez-Sanchez and colleagues demonstrate in cultured mammalian cells and in fruit fly larvae that autophagy is regulated by Hedgehoc signalling, a pathway that is important for early embryonic development.
- Maria Jimenez-Sanchez
- , Fiona M. Menzies
- & David C. Rubinsztein
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A peptide derived from laminin-γ3 reversibly impairs spermatogenesis in rats
The temporal opening and closing of cell–cell junctions at the blood–testis barrier allows the passage of immature germ cells during spermatogenesis. Su and colleagues identify a peptide fragment of the laminin-γ3 chain that disrupts the blood–testis barrier and reversibly impairs spermatogenesis in rats.
- Linlin Su
- , Dolores D. Mruk
- & C. Yan Cheng
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Lfng regulates the synchronized oscillation of the mouse segmentation clock via trans-repression of Notch signalling
The mouse segmentation clock regulates the periodicity of somite formation. Okubo and colleagues investigate the mechanisms underlying the synchronization of the clock in embryonic chimaeras and find that the synchronization is regulated by the protein Lfng, which represses Notch signalling in neighbouring cells.
- Yusuke Okubo
- , Takeshi Sugawara
- & Yumiko Saga
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Insight into the early evolution of the avian sternum from juvenile enantiornithines
The keeled sternum is a distinct skeletal element in extant birds. In this study, specimens of juvenile extinct birds—Enantiornithes—from the Early Cretaceous show a unique sequence of development in the sternum, suggesting differences between living birds and this extinct clade.
- Xiaoting Zheng
- , Xiaoli Wang
- & Zhonghe Zhou
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| Open AccessEndogenous Wnt signalling in human embryonic stem cells generates an equilibrium of distinct lineage-specified progenitors
Human embryonic stem cell cultures are morphologically heterogeneous. Here, differences in Wnt signalling are shown to contribute to this heterogeneity, cells containing high levels of Wnt form endodermal and cardiac cells, whereas cells with low Wnt form neuroectodermal cells, when differentiation is induced.
- Timothy A. Blauwkamp
- , Shelly Nigam
- & Roel Nusse
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Delivery of endosomes to lysosomes via microautophagy in the visceral endoderm of mouse embryos
Nutrients and growth factors initiate endocytotic processes in the embryonic endoderm that control embryonic patterning. Here, Kawamuraet al.show that the small GTP-binding protein rab7 controls a unique microautophagy-like process that is involved in endocytosis in the endoderm of mouse embryos.
- Nobuyuki Kawamura
- , Ge-Hong Sun-Wada
- & Yoh Wada
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| Open AccessHigh-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer risk in several generations of offspring
Environmental factors can influence one's susceptibility to cancer, but it is not clear whether such an influence extends beyond the directly exposed generations. Here, feeding pregnant rats with a high-fat diet or a hormone derivative, the authors observe increased breast cancer risk in up to three subsequent generations.
- Sonia de Assis
- , Anni Warri
- & Leena Hilakivi-Clarke
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The amniote paratympanic organ develops from a previously undiscovered sensory placode
The paratympanic organ in the avian middle ear is similar to the fish spiracular organ, but its developmental origin is unresolved. O'Neillet al. use fate mapping techniques to show that the avian paratympanic organ and its afferent neurons arise from a previously undiscovered neurogenic placode.
- Paul O'Neill
- , Siu-Shan Mak
- & Clare V.H. Baker
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| Open AccessUnfolded protein response, activated by OASIS family transcription factors, promotes astrocyte differentiation
The protein OASIS belongs to the CREB/ATF transcription factor family and is involved in endoplasmic reticulum stress responses. Saito and colleagues show that these stress responses temporally activate OASIS in neural precursor cells, resulting in their differentiation into astrocytes.
- Atsushi Saito
- , Soshi Kanemoto
- & Kazunori Imaizumi
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Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation
Embryonic stem cells have a shortened cell cycle that allows for rapid proliferation, but the exact mechanisms are unclear. Here, a microRNA target, Trim71, is shown to inhibit the expression of a cyclin-dependent kinase inhibitor, thus enabling the G1–S phase cell cycle transition in embryonic stem cells.
- Hao-Ming Chang
- , Natalia J. Martinez
- & Richard I. Gregory
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Histone modifications and lamin A regulate chromatin protein dynamics in early embryonic stem cell differentiation
Chromatin in embryonic stem cells is present in an open state presumably to facilitate gene expression changes required for pluripotency and subsequent multilineage differentiation. This study describes roles for lamin A, histone acetylation and G9a-mediated histone H3 lysine 9 methylation in regulating chromatin plasticity in these cells.
- Shai Melcer
- , Hadas Hezroni
- & Eran Meshorer
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| Open AccessTracing back the nascence of a new sex-determination pathway to the ancestor of bees and ants
In several Hymenoptera species - ants, bees and wasps - sexual fate is determined by the allelic composition at the complementary sex - determiner locus. This study identifies the honeybeecomplementary sex - determinerin bumble bee and ant orthologues, previously thought to be unique to the honeybee lineage.
- Sandra Schmieder
- , Dominique Colinet
- & Marylène Poirié
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O-glycosylation modulates integrin and FGF signalling by influencing the secretion of basement membrane components
Altered O-glycosylation of proteins is implicated in various human diseases. In this study, Tian and co-workers study mice that are deficient in the O-glycosylation enzyme Galnt1, and find reduced cell proliferation and organogenesis as well as increased endoplasmic reticulum stress.
- E. Tian
- , Matthew P. Hoffman
- & Kelly G. Ten Hagen
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| Open AccessThe Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility
The non-canonical Wnt signalling pathway mediates cell migration via the GTPase Rac but the detailed mechanism is unclear. In this study, the Daple protein is shown to regulate Wnt5a mediated activation of Rac, resulting in the formation of lamellipodia and cell migration.
- Maki Ishida-Takagishi
- , Atsushi Enomoto
- & Masahide Takahashi
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Microtubule and cortical forces determine platelet size during vascular platelet production
Platelets are formed from megakaryocytes but the exact mechanisms are unknown. Thonet al.describe circular preplatelets and barbell shaped proplatelets in human blood and demonstrate, with the aid of a mathematical model, a role for microtubule-based forces in regulating final platelet size.
- Jonathan N Thon
- , Hannah Macleod
- & Joseph E. Italiano Jr
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Article
| Open AccessActivin induces cortical interneuron identity and differentiation in embryonic stem cell-derived telencephalic neural precursors
Signalling inputs to neural progenitors regulate the differentiation of the stem cell pool. By analysing the mechanisms occuring during neurogenesis, Cambrayet al. report that activin is the pivotal factor regulating the differentiation of telencephalic neural precursors towards a cortical interneuron fate.
- Serafí Cambray
- , Charles Arber
- & Tristan A. Rodríguez
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| Open AccessJAK/STAT3 signalling is sufficient and dominant over antagonistic cues for the establishment of naive pluripotency
Culture conditions are critical for the successful induction of pluripotent stem cells and define whether cells are primed or naïve. Here, activation of JAK/STAT3 signalling is shown to be sufficient and dominant over antagonistic cues to enable the induction of a naïve pluripotent state in stem cells.
- Anouk L. van Oosten
- , Yael Costa
- & José C.R. Silva
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Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster
Hox gene expression is induced upon cellular differentiation and is inhibited in pluripotent cells. Bocker and colleagues show that the maintenance of induced transcription depends on Tet2 mediated hydroxylation of 5-methylcytosine at theHoxagene locus, indicating that this epigenetic switch is required for an active chromatin state and gene expression.
- Michael T. Bocker
- , Francesca Tuorto
- & Achim Breiling
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Article
| Open AccessFully functional hair follicle regeneration through the rearrangement of stem cells and their niches
Bioengineered hair follicles can be produced from embryonic follicle germ cells, but whether these follicles can interact with the surrounding tissue and function normally is unknown. Here, bioengineered hair follicles transplanted into mouse dermis make connections with the surrounding tissue and show normal hair cycles.
- Koh-ei Toyoshima
- , Kyosuke Asakawa
- & Takashi Tsuji
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Drosophila follicle stem cells are regulated by proliferation and niche adhesion as well as mitochondria and ROS
Stem cells are thought to be tethered in their niche via adhesion molecules and the inhibition of cell differentiation. Here, the authors screened for genes required for maintainingDrosophilaovarian follicle stem cells and found their function to depend on cell proliferation, mitochondrial function and niche adhesion.
- Zhu A. Wang
- , Jianhua Huang
- & Daniel Kalderon
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Poly(ADP-ribose) controls DE-cadherin-dependent stem cell maintenance and oocyte localization
Drosophilagermline stem cells are anchored to their niche via DE-cadherin. In this study, poly(ADP-ribose) is shown to regulate the expression of DE-cadherin via the heterogeneous nuclear ribonucleoprotein, hnRNPA1, and defects in poly(ADP-ribose) catabolism or hnRNPA1 deficiency lead to the loss of germline stem cells.
- Yingbiao Ji
- & Alexei V. Tulin
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| Open AccessUnique domain appended to vertebrate tRNA synthetase is essential for vascular development
Seryl-tRNA synthetase is important in vasculogenesis and contains a unique domain at its C-terminus. In this study, the unique domain is shown to target the protein to the nucleus, block expression ofvegfaand be essential for vasculogenesis in zebrafish.
- Xiaoling Xu
- , Yi Shi
- & Xiang-Lei Yang
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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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Homeostatic neurogenesis in the adult hippocampus does not involve amplification of Ascl1high intermediate progenitors
Neural stem cells generate neurons in the adult hippocampus, but the dynamics of neuron production remain unclear. This study shows that stem cells produce type-2a progenitors, which do not expand as previously thought, but rather generate amplifying immature neuroblasts.
- Sebastian Lugert
- , Miriam Vogt
- & Verdon Taylor
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