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| Open AccessLin28 and let-7 regulate the timing of cessation of murine nephrogenesis
Nephrogenesis ceases after postnatal day 2 in the mouse or after the 36th week of gestation in humans, but how this is regulated is unclear. Here, the authors identify a role for the RNA-binding protein Lin28 and suppression of let-7 microRNA in regulating the duration of nephrogenesis.
- Alena V. Yermalovich
- , Jihan K. Osborne
- & George Q. Daley
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Article
| Open AccessSingle-molecule imaging correlates decreasing nuclear volume with increasing TF-chromatin associations during zebrafish development
Zygotic genome activation (ZGA), the onset of transcription after initial quiescence, is a major developmental step in many species. Here authors use single molecule tracking in live developing zebrafish embryos to show that increased transcription factor binding to DNA at ZGA is due to a shrinking nucleus.
- Matthias Reisser
- , Anja Palmer
- & J. Christof M. Gebhardt
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Article
| Open AccessDynamic and non-contact 3D sample rotation for microscopy
Sample orientation is crucial to ensure optimal image quality in light microscopy. Here the authors enable multi-axis orientation of fixed mouse embryos and shrimp, and live zebrafish embryos and larvae by introducing magnetic beads and rotating the sample with a magnetic field in a microscope.
- Frederic Berndt
- , Gopi Shah
- & Jan Huisken
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Article
| Open AccessLoss of embryonic neural crest derived cardiomyocytes causes adult onset hypertrophic cardiomyopathy in zebrafish
A small percentage of cardiomyocytes (CM) are of neural crest origin but the function of such cells in the adult zebrafish is unclear. Here, the authors identify this CM subpopulation as expressing the Notch ligand jag2b and if deleted in the embryo, cause severe hypertrophic cardiomyopathy in adulthood.
- Sarah Abdul-Wajid
- , Bradley L. Demarest
- & H. Joseph Yost
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Article
| Open AccessTracing the transitions from pluripotency to germ cell fate with CRISPR screening
Primordial Germ Cell-Like Cells (PGCLCs) are an in vitro model for primordial germ cell development. Here, the authors couple a novel compound reporter with CRISPR screening to identify key genes for exit from pluripotency and acquisition of PGCLC fate; specifically identifying Nr5a2 and Zfp296.
- Jamie A. Hackett
- , Yun Huang
- & M. Azim Surani
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Article
| Open AccessCFP1 coordinates histone H3 lysine-4 trimethylation and meiotic cell cycle progression in mouse oocytes
The transcription-independent function of trimethylation of histone H3 (H3K4me) in cell division is unclear. Here, Heng-Yu Fan and colleagues report that CFP1, a subunit of the H3K4 methyltransferase, is required for oocyte meiosis, being phosphorylated and degraded during cell cycle transition.
- Qian-Qian Sha
- , Xing-Xing Dai
- & Heng-Yu Fan
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Article
| Open AccessLTR retrotransposons transcribed in oocytes drive species-specific and heritable changes in DNA methylation
De novo DNA methylation during mouse oogenesis occurs within transcribed regions. Here the authors investigate the role of species-specific long terminal repeats (LTRs)-initiated transcription units in regulating the oocyte methylome, identifying syntenic regions in mouse, rat and human with divergent DNA methylation associated with private LITs.
- Julie Brind’Amour
- , Hisato Kobayashi
- & Matthew C. Lorincz
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Article
| Open AccessEmbryos and embryonic stem cells from the white rhinoceros
The Southern (SWR) and Northern (NWR) are two subspecies of the White Rhinoceros with the NWR being almost extinct. Here, using assisted reproduction technology, the authors produce and cryopreserve SWR purebred and NWR-SWR hybrid embryos developed to the blastocyst stage, and also generate embryonic stem cell lines, in an attempt to save genes of the NWR.
- Thomas B. Hildebrandt
- , Robert Hermes
- & Cesare Galli
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Article
| Open AccessUterine glands coordinate on-time embryo implantation and impact endometrial decidualization for pregnancy success
The transcription factor FOXA2 is specifically expressed in uterine glands. Here, using two conditional FOXA2 knockout mouse models, the authors show that glandular epithelia of the endometrium are required for timely embryo implantation and subsequent endometrial decidualization during successful pregnancy establishment.
- Andrew M. Kelleher
- , Jessica Milano-Foster
- & Thomas E. Spencer
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Article
| Open AccessGuided morphogenesis through optogenetic activation of Rho signalling during early Drosophila embryogenesis
Optogenetics is opening the possibility to not only perturb morphogenesis, but also to guide it. Here, the authors use this technique to reconstruct epithelial folding in Drosophila embryos and study the relationship between strength of Rho activation, apical constrictions, and tissue invagination.
- Emiliano Izquierdo
- , Theresa Quinkler
- & Stefano De Renzis
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Article
| Open AccessParental haplotype-specific single-cell transcriptomics reveal incomplete epigenetic reprogramming in human female germ cells
In mammalian female germ cells, parent-specific epigenetic marks are erased and the X chromosome reactivated before entry into meiosis. Here, by combining parental haplotype reconstruction with single-cell transcriptomics of human female embryonic germ cells, the authors demonstrate that epigenetic reprogramming occurs in a heterogeneous fashion and during a broad time window up to week 14.
- Ábel Vértesy
- , Wibowo Arindrarto
- & Susana M. Chuva de Sousa Lopes
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Perspective
| Open AccessTracing the origin of heterogeneity and symmetry breaking in the early mammalian embryo
What breaks symmetry in early mammalian embryonic development has been much questioned. Here, Magdalena Zernicka-Goetz and colleagues propose that compartmentalized intracellular reactions generate micro-scale inhomogeneity, which is amplified in the developing embryo, driving pattern formation.
- Qi Chen
- , Junchao Shi
- & Magdalena Zernicka-Goetz
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Article
| Open AccessP53 and mTOR signalling determine fitness selection through cell competition during early mouse embryonic development
During embryo development, cell fitness determines survival but how this is regulated is unclear. Here, the authors show that in early embryonic development and stem cells exiting the naive state, cells sense the fitness of their neighbours and trigger p53 to repress mTOR to eliminate a third of cells.
- Sarah Bowling
- , Aida Di Gregorio
- & Tristan A. Rodríguez
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Article
| Open AccessTrue equilibrium measurement of transcription factor-DNA binding affinities using automated polarization microscopy
Methods to measure selective transcription factor-DNA binding often lack sensitivity and are not performed in solution. Here the authors develop a method to perform fluorescence anisotropy measurements of transcription factor-DNA binding energies with high sensitivity and throughput.
- Christophe Jung
- , Peter Bandilla
- & Ulrike Gaul
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Article
| Open AccessGlycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus
Defects in neural crest development cause neurocristopathies and cancer, but what regulates this is unclear. Here, the authors show that glycogen synthase kinase 3 (GSK3) regulates migration of neural crest cells, as shown on genetic deletion of GSK3 in the mouse, and that this acts via anaplastic lymphoma kinase.
- Sandra G. Gonzalez Malagon
- , Anna M. Lopez Muñoz
- & Karen J. Liu
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Article
| Open AccessTridimensional visualization reveals direct communication between the embryo and glands critical for implantation
Embryo implantation initiates the interaction of the blastocyst with the uterus and occurs within a specialised crypt formed by uterine epithelial cells. Here, using 3D imaging techniques of wild type and mutant uteri, the authors show that crypt formation occurs with preexisting glands of the uterus, opening communication between glands and the implanting embryo.
- Jia Yuan
- , Wenbo Deng
- & Sudhansu. K. Dey
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Article
| Open AccessRoles of two types of heparan sulfate clusters in Wnt distribution and signaling in Xenopus
Wnt proteins mediate embryonic development but how protein localization and patterning is regulated is unclear. Here, the authors show that distinct structures with different heparan sulfate modifications (‘N-sulfo-rich’ and ‘N-acetyl-rich’) regulate cellular localization and signal transduction of Wnt8 in Xenopus.
- Yusuke Mii
- , Takayoshi Yamamoto
- & Masanori Taira
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Article
| Open AccessCytoplasmic cleavage of DPPA3 is required for intracellular trafficking and cleavage-stage development in mice
During the maternal-to-zygotic transition there is degradation of maternal proteins via the ubiquitin-proteasome system (UPS). Here, the authors show that in the embryo the maternally inherited epigenetic factor DPPA3/Stella/PGC7 is cleavage by the UPS and controls intracellular trafficking.
- Seung-Wook Shin
- , Edgar John Vogt
- & Jurrien Dean
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Article
| Open AccessSpatial regulation of contractility by Neuralized and Bearded during furrow invagination in Drosophila
In the Drosophila embryo, increased cortical contractility in ventral cells causes furrow formation and gastrulation. Here, the authors show that contractility is regulated by Neuralized (an E3 ubiquitin ligase) in ventral cells, and that inhibiting this process with Bearded in the ectoderm causes furrow invagination.
- Gantas Perez-Mockus
- , Khalil Mazouni
- & François Schweisguth
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Article
| Open AccessBoth Nodal signalling and stochasticity select for prospective distal visceral endoderm in mouse embryos
In the mouse embryo, anterior-posterior polarity is established by distal visceral endoderm (DVE) at embryonic day 5.5 but how this arises is unclear. Here, the authors show that expression of Lefty1 earlier can define DVE, and that future DVE cells are selected by Nodal signalling and stochasticity.
- Katsuyoshi Takaoka
- , Hiromi Nishimura
- & Hiroshi Hamada
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Article
| Open AccessThe WHHERE coactivator complex is required for retinoic acid-dependent regulation of embryonic symmetry
Retinoic acid (RA) regulates the maintenance of somitogenesis symmetry. Here, the authors use a proteomic approach to identify a protein complex of Wdr5, Hdac1, Hdac2 that act together with RA and coactivator Rere/Atrophin2 and a histone methyltransferase Ehmt2 to regulate embryonic symmetry.
- Gonçalo C. Vilhais-Neto
- , Marjorie Fournier
- & Olivier Pourquié
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Article
| Open AccessDecidualisation and placentation defects are a major cause of age-related reproductive decline
Advanced maternal age has been associated with lower reproductive success and higher risk of pregnancy complications. Here the authors show that maternal ageing-related embryonic abnormalities in mouse are caused by decidualisation and placentation defects that can be rescued by transferring the embryo from an old to a young uterus.
- Laura Woods
- , Vicente Perez-Garcia
- & Myriam Hemberger
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Article
| Open AccessA pluripotent stem cell-based model for post-implantation human amniotic sac development
Early in human embryonic development, it is unclear how amniotic sac formation is regulated. Here, the authors use a human pluripotent stem cell-based model, termed the post-implantation amniotic sac embryoid, to recapitulate early embryogenic events of human amniotic sac development.
- Yue Shao
- , Kenichiro Taniguchi
- & Jianping Fu
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Article
| Open AccessSorting at embryonic boundaries requires high heterotypic interfacial tension
The mechanisms that cause different cells to segregate into distinct tissues are unclear. Here the authors show in Xenopus that formation of a boundary between two tissues is driven by local tension along the interface rather than by global differences in adhesion or cortical contractility.
- Laura Canty
- , Eleyine Zarour
- & François Fagotto
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Article
| Open AccessCo-option of the cardiac transcription factor Nkx2.5 during development of the emu wing
The transcription factor Nkx2.5 is essential for heart development. Here, the authors identify a previously unknown expression domain for Nkx2.5 in the emu wing and explore its role in diminished wing bud development in the flightless emu, compared with three other birds that have functional wings.
- Peter G. Farlie
- , Nadia M. Davidson
- & Craig A. Smith
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Article
| Open AccessExtra-embryonic tissue spreading directs early embryo morphogenesis in killifish
The role of mechanical signals in early development are not fully understood. Here, the authors use the simplicity of early killifish embryos to show that tension arising from extra-embryonic epithelial expansion directs the spreading of mesenchymal-like embryonic cells during early morphogenesis.
- Germán Reig
- , Mauricio Cerda
- & Miguel L. Concha
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Article
| Open AccessAn extra-uterine system to physiologically support the extreme premature lamb
The ability to support the development of a premature fetus in the form of an extracorporeal system has had limited success. Here, the authors show that an extra-uterine device that mimics the intra-uterine environment can provide physiologic support for the extreme premature lamb fetus for four weeks.
- Emily A. Partridge
- , Marcus G. Davey
- & Alan W. Flake
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Article
| Open AccessFoxa2 identifies a cardiac progenitor population with ventricular differentiation potential
The progenitor populations that contribute to the key cardiac lineages in a chamber-specific manner are unknown. Here, the authors identifyFoxa2+ progenitor population, which is specified at gastrulation, as contributing primarily to cardiovascular cells of both ventricles and the epicardium in mice.
- Evan Bardot
- , Damelys Calderon
- & Nicole C. Dubois
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Article
| Open AccessDpath software reveals hierarchical haemato-endothelial lineages of Etv2 progenitors based on single-cell transcriptome analysis
Single-cell RNA sequencing has enabled great advances in understanding developmental biology but reconstructing cellular lineages from this data remains challenging. Here the authors develop an algorithm,dpath, which models the lineage relationships of underlying single cells based on single cell RNA seq data and apply it to study lineage progression of Etv2 expressing progenitors.
- Wuming Gong
- , Tara L. Rasmussen
- & Daniel J. Garry
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Article
| Open AccessA cell-based computational model of early embryogenesis coupling mechanical behaviour and gene regulation
Embryonic development is a complex process where genetic and biochemical information direct morphogenesis. Here the authors describe MecaGen, an agent-based model and simulation platform of multicellular development designed to allow a quantitative comparison between simulations and real biological data.
- Julien Delile
- , Matthieu Herrmann
- & René Doursat
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Article
| Open AccessInfrared laser-induced gene expression for tracking development and function of single C. elegans embryonic neurons
Tools to label single neurons and track their development inC. elegans have been lacking. Singhal et al. optimized a method, which applies infrared laser to induce heat-dependent gene expression at cellular resolution in developing C. elegansembryos, and show that it can uncover new aspects of embryo morphogenesis.
- Anupriya Singhal
- & Shai Shaham
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Article
| Open AccessAsynchronous fate decisions by single cells collectively ensure consistent lineage composition in the mouse blastocyst
Early embryonic cell fate and lineage specification is tightly regulated in the preimplantation mammalian embryo. Here, the authors quantitatively examine the ratio of epiblast to primitive endoderm lineages in the blastocyst and show composition of the inner cell mass is conserved, independent of its size.
- Néstor Saiz
- , Kiah M. Williams
- & Anna-Katerina Hadjantonakis
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Article
| Open AccessAbundant DNA 6mA methylation during early embryogenesis of zebrafish and pig
DNA 6mA is a poorly understood epigenetic mark present at a low abundance in eukaryotic genomes. Here the authors observe high levels in zebrafish and pig during early embryogenesis enriched to repetitive regions of the genome and followed by attenuation during development.
- Jianzhao Liu
- , Yuanxiang Zhu
- & Chuan He
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Article
| Open AccessCripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency
Stem cell plasticity is crucial for early embryo development and the differentiation of stem cells. Here, the authors show that the extracellular protein Cripto sustains mouse ESC self-renewal and maintains mouse EpiSC as well as human ESC pluripotency and controls the metabolic reprogramming in ESCs to EpiSC transition.
- Alessandro Fiorenzano
- , Emilia Pascale
- & Gabriella Minchiotti
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Article
| Open AccessKinetics and specificity of paternal mitochondrial elimination in Caenorhabditis elegans
Autophagy mediates the degradation of paternal mitochondria after fertilization in C. elegansto ensure that mitochondria are inherited maternally. Here the authors show that mitochondrial dynamics is critical for the selectivity and kinetics of paternal mitochondrial elimination.
- Yang Wang
- , Yi Zhang
- & Ding Xue
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Article
| Open AccessFscn1 is required for the trafficking of TGF-β family type I receptors during endoderm formation
It is unclear how the cytoskeleton acts to assist in TGF-β signalling downstream of the receptor. Here, in zebrafish, the authors show that the actin-bundling protein FSCN1 interacts with TGF-β type I receptors ALK 4 and 5, enabling actin filament mediated vesicle trafficking and endoderm formation.
- Zhaoting Liu
- , Guozhu Ning
- & Qiang Wang
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Article
| Open AccessBMP and retinoic acid regulate anterior–posterior patterning of the non-axial mesoderm across the dorsal–ventral axis
It is unclear how the dorsal-ventral (DV) and anterior-posterior (AP) axes established in the gastrula affect tissues. Here, the authors show that in zebrafish kidney development, with regard to non-axial mesoderm, the classic DV axis corresponds to the AP axis, and is regulated by BMP and retinoic acid.
- Richard W. Naylor
- , Lauren Brilli Skvarca
- & Alan J. Davidson
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Article
| Open AccessGlobal changes of the RNA-bound proteome during the maternal-to-zygotic transition in Drosophila
Early development is controlled by maternally deposited mRNAs and the RNA-binding proteins (RBPs) that regulate them. Here the authors describe the identification of a large number of RBPs bound to polyadenylated RNAs in Drosophilaembryos before and after the maternal-to-zygotic transition, revealing changes in RBPs activity during development.
- Vasiliy O. Sysoev
- , Bernd Fischer
- & Anne Ephrussi
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Article
| Open AccessEssential role of the TFIID subunit TAF4 in murine embryogenesis and embryonic stem cell differentiation
The role of TFIID core module TAFs (TATA-binding protein-associated factors) in embryogenesis is unknown. Here, the authors show that Taf4 is essential at mid-gestation and for complete neuronal differentiation of embryonic stem cells, but that Taf4a and Taf4b are redundant at early embryonic stages.
- Diana Langer
- , Igor Martianov
- & Irwin Davidson
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Article
| Open AccessMouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential
The developmental potential of mosaic embryos of euploid and aneuploid cells is unknown. Here, the authors create a mouse model of chromosome mosaicism, showing that aneuploid cells in the fetus are eliminated by apoptosis and developmental potential is dependent on the presence of sufficient euploid cells.
- Helen Bolton
- , Sarah J. L. Graham
- & Magdalena Zernicka-Goetz
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Article
| Open AccessA workflow to process 3D+time microscopy images of developing organisms and reconstruct their cell lineage
Quantitative analysis of embryonic cell dynamics from large data sets remains a major challenge in the field of developmental biology. Here the authors develop software and a workflow to reconstruct cell lineage trees from 3D time lapse imaging data sets from several developing organisms including zebrafish, tunicates and sea urchins.
- Emmanuel Faure
- , Thierry Savy
- & Paul Bourgine
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Article
| Open AccessHuman oocyte developmental potential is predicted by mechanical properties within hours after fertilization
Reliable assessments of oocyte developmental potential are lacking, making it difficult to select the best quality embryos for transfer after in vitrofertilization. Here, the authors show that a non-invasive measurement of viscoelastic properties predicts developmental potential in both humans and mice.
- Livia Z. Yanez
- , Jinnuo Han
- & David B. Camarillo
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Article
| Open AccessA short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells
In fast proliferating embryonic stem cells (ESC) the DNA damage response is activated by mechanisms that are as yet elusive. Here, Ahuja et al.link the DNA damage response to replication stress in mouse ESCs, caused by a short G1 phase, and propose fork remodelling as maintaining genome stability in embryos.
- Akshay K. Ahuja
- , Karolina Jodkowska
- & Massimo Lopes
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Article
| Open AccessNotch signal strength controls cell fate in the haemogenic endothelium
It is unclear how Notch1 signals regulate both the maintenance of the endothelial fate and the endothelial-to-hematopoietic transition in the embryonic aorta. Here the authors show that those cells in which Notch1 ligand Jag1 is out-competed by Dll4 remain endothelial, while higher Jag1 activity leads to generation of hematopoietic stem cells.
- Leonor Gama-Norton
- , Eva Ferrando
- & Anna Bigas
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Article
| Open AccessDrosophila germ granules are structured and contain homotypic mRNA clusters
What regulates mRNAs transcript localization in the germ granules in Drosophila is unclear. Here Trcek et al.identify that germ plasm proteins are homogeneously distributed in germ granules but once localized, individual mRNAs form homotypic clusters, contributing structure to the germ granules.
- Tatjana Trcek
- , Markus Grosch
- & Ruth Lehmann
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Article
| Open AccessTwo routes to senescence revealed by real-time analysis of telomerase-negative single lineages
Erosion of telomeres eventually causes replicative senescence, but mechanisms underlying the variability and dynamics of the pathway are not known. Here, the authors examine senescence in single yeast cells with inactivated telomerase to reveal two mechanistically distinct routes to senescence.
- Zhou Xu
- , Emilie Fallet
- & Maria Teresa Teixeira
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Article
| Open AccessPrediction model for aneuploidy in early human embryo development revealed by single-cell analysis
Aneuploidy may be fatal for the embryo, hence predicting its occurrence is important for successfulin vitrofertilization. Here the authors monitor development of human preimplantation embryos in real-time and correlate the blastomere ploidy with cleavage dynamics and gene expression, identifying 12-transcript signature that determines ploidy.
- Maria Vera-Rodriguez
- , Shawn L. Chavez
- & Carlos Simon
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Article |
Changing cell behaviours during beetle embryogenesis correlates with slowing of segmentation
Sequential segmentation in development is best described in vertebrates, where it relies on cell proliferation and shows regular periodicity. Here, the authors show that in the flour beetle segments are added with irregular rate and their elongation during periods of fast growth relies mostly on cell movements.
- A. Nakamoto
- , S. D. Hester
- & T. A. Williams
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Article |
A cohesin–OCT4 complex mediates Sox enhancers to prime an early embryonic lineage
Higher order chromatin structures affect gene transcription, but how they determine cell fate is unclear. Here, the authors show that OCT4 and SALL4 alter the higher-order chromatin structure and mediate cell fate switching in embryonic cells by targeting cohesin and polycomb complexes, respectively.
- Nesrine Abboud
- , Thomas Moore- Morris
- & Michel Pucéat