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Article
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Endocardial HDAC3 is required for myocardial trabeculation
Lack of trabeculation compromises heart structure and function. How myocardial trabeculation is regulated by nonmyocytes is poorly understood. Researchers found that histone deacetylase 3 in the developing endocardial cells guides myocardial trabeculation by inducing growth signals.
- Jihyun Jang
- , Mette Bentsen
- & Deqiang Li
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| Open Access
Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis
MAPK-driven tumorigenesis is often related to epithelial dedifferentiation but the regulatory mechanism is less clear. Here, the authors show that MAPK activation upregulates USP15 to promote deubiquitylation and stability of TBX3, a transcription factor implicated in thyroid development and differentiation, driving tumorigenesis in a BRAFV600E thyroid tumor model.
- Zhenlei Zhang
- , Yufan Wu
- & Li Zhao
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| Open Access
Cell-type-specific mRNA transcription and degradation kinetics in zebrafish embryogenesis from metabolically labeled single-cell RNA-seq
This study analyzes the embryonic replacement of maternally contributed mRNA with new mRNA in single cells and shows dynamic spatio-temporal regulation of maternal mRNA decay and cell-type specific retention within the earliest specified cell types in zebrafish embryos.
- Lior Fishman
- , Avani Modak
- & Michal Rabani
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Eph-ephrin signaling couples endothelial cell sorting and arterial specification
Arteries are vital blood vessels for our body and their growth and patterning are critical for proper blood flow. Here they use a retina model to show that a balance of EphB4 receptor and ephrin-B2 ligand integrate a well-wired molecular network to control arteriovenous patterning and vascular growth.
- Jonas Stewen
- , Kai Kruse
- & Mara E. Pitulescu
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Temporospatial hierarchy and allele-specific expression of zygotic genome activation revealed by distant interspecific urochordate hybrids
Wei et al. report a unique interspecific ascidian hybrid system and single-cell RNA sequencing to reveal the temporal hierarchy, spatial heterogeneity, and allele-specific expression of zygotic genome activation in urochordates.
- Jiankai Wei
- , Wei Zhang
- & Bo Dong
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| Open Access
A single-cell atlas of Drosophila trachea reveals glycosylation-mediated Notch signaling in cell fate specification
Studying Drosophila trachea development can inform the mechanisms of growth of all tubular structures. Here, the authors generate a transcriptomic cell atlas of the developing fly trachea and establish roles for Notch signaling, which may be disrupted by diet-induced glycosylation.
- Yue Li
- , Tianfeng Lu
- & Hai Huang
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| Open Access
Single-cell multiomics decodes regulatory programs for mouse secondary palate development
Development of the secondary palate is a complex process. Here, the authors profile mouse palatogenesis through single-cell multiome sequencing, revealing dynamic gene regulation across embryonic days (E) 12.5, E13.5, E14.0, and E14.5.
- Fangfang Yan
- , Akiko Suzuki
- & Zhongming Zhao
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LinRace: cell division history reconstruction of single cells using paired lineage barcode and gene expression data
Inferring lineage trees while incorporating gene expressions and lineage barcodes is a challenging task. Here, authors present LinRace, which infers improved cell lineage trees and ancestral cell states using the proposed asymmetric division model.
- Xinhai Pan
- , Hechen Li
- & Xiuwei Zhang
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| Open Access
Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands
Rocha and co-authors show that loss of luminal Rank signaling causes abnormal alveolar differentiation and lactation failure. Subsequent pregnancies activate bipotency in basal cells, replacing unfit luminal cells, and restoring lactation.
- Ana Sofia Rocha
- , Alejandro Collado-Solé
- & Eva González-Suárez
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Maintenance of pluripotency-like signature in the entire ectoderm leads to neural crest stem cell potential
How the neural crest gains its pluripotency-like stem cell potential is unclear. Here, the authors show that the entire post-gastrula ectoderm maintains expression of pluripotency genes, leading to the high stem cell capacity in the neural crest.
- Ceren Pajanoja
- , Jenny Hsin
- & Laura Kerosuo
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| Open Access
Placental growth factor exerts a dual function for cardiomyogenesis and vasculogenesis during heart development
Growth factors play key roles during heart development. Here they show that PLGF has both autocrine and paracrine roles during cardiomyogenesis and vasculogenesis, suggesting it may have therapeutic potential for heart disease.
- Nevin Witman
- , Chikai Zhou
- & Makoto Sahara
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Article
| Open Access
Apicobasal RNA asymmetries regulate cell fate in the early mouse embryo
How do cells of the preimplantation mouse embryo make decisions? Here the authors discovered that the spatial sorting of mRNAs, tRNA, rRNAs and organelles lead to localized translation, conducive for cell fate allocation and embryonic development.
- Azelle Hawdon
- , Niall D. Geoghegan
- & Jennifer Zenker
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| Open Access
Establishment of gastrointestinal assembloids to study the interplay between epithelial crypts and their mesenchymal niche
Most intestinal organoid models do not accurately model the interactions between epithelial and stromal cells. Here they establish a colon assembloid system with epithelial and stromal cells and demonstrate that BMP signals from differentiating epithelial cells promote mesenchymal niche organization.
- Manqiang Lin
- , Kimberly Hartl
- & Michael Sigal
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| Open Access
Mechanisms and function of de novo DNA methylation in placental development reveals an essential role for DNMT3B
DNA methylation is a repressive modification that is essential for development. Here the authors reveal a critical role for DNA methylation in placental development during pregnancy. Failure to properly establish placental DNA methylation patterns compromises not only placental function, but embryo survival.
- Simon Andrews
- , Christel Krueger
- & Courtney W. Hanna
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Large-scale perfused tissues via synthetic 3D soft microfluidics
Bioengineering live tissues has remained challenging due to limited nutrient exchange in the growing tissues. Here, the authors have developed micro-perfused 2-photon printing of 3D microfluidics, to engineer large-scale, viable and functional neural and hepatic 3D tissues.
- Sergei Grebenyuk
- , Abdel Rahman Abdel Fattah
- & Adrian Ranga
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| Open Access
Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis
Regulation of oriented cell divisions during development is important to position daughter cells and build a structured and functional tissue. Here the authors show that Annexin A1 is a key polarity protein that regulates planar orientation of the cell division axis to guide mammary epithelial morphogenesis.
- Maria Fankhaenel
- , Farahnaz S. Golestan Hashemi
- & Salah Elias
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| Open Access
In vivo clonal tracking reveals evidence of haemangioblast and haematomesoblast contribution to yolk sac haematopoiesis
The lineage relationship between blood and endothelial cells has been difficult to examine due to the multiphasic timing of hematopoiesis in the embryo. Here the authors use using in vivo barcoding technology to assess cell ancestry and show that blood and endothelial cells emerge through common (haemangioblast) or separate (mesenchymoangioblasts and haematomesoblasts) progenitors in the yolk sac.
- C. Biben
- , T. S. Weber
- & S. Taoudi
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| Open Access
Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling
Here the authors show that FGF signaling initiates alveolus development in mouse lung by inducing AT2 fate and a secondary signal for AT1 fate, and continuously maintains AT2 cells throughout life. FGF inhibition triggers immediate AT2 apoptosis and compensatory regeneration.
- Douglas G. Brownfield
- , Alex Diaz de Arce
- & Mark A. Krasnow
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Human multilineage pro-epicardium/foregut organoids support the development of an epicardium/myocardium organoid
Stem cell models of organogenesis are a valuable tool for the study of human development, but often lack the context of tissue-tissue interaction. Here they generate human multi-lineage organoids comprising pro-epicardium, septum transversum, and liver bud, which they co-culture with heart organoids to generate a physiologically relevant model of organogenesis.
- Mariana A. Branco
- , Tiago P. Dias
- & Maria Margarida Diogo
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| Open Access
The TFEB-TGIF1 axis regulates EMT in mouse epicardial cells
Epithelial-mesenchymal transition (EMT) is a complex process involved in organogenesis. Here, the authors show that the transcription factor EB (TFEB) regulates EMT in epicardium during heart development by tuning sensitivity to TGFβ signaling.
- Elena Astanina
- , Gabriella Doronzo
- & Federico Bussolino
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Spatiotemporal single-cell regulatory atlas reveals neural crest lineage diversification and cellular function during tooth morphogenesis
The mechanisms that govern cell fate decisions of postmigratory cranial neural crest cells remain largely unknown. Here the authors present a spatiotemporal single-cell regulatory atlas tracking these cells’ dental lineage diversification.
- Junjun Jing
- , Jifan Feng
- & Yang Chai
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| Open Access
A hexa-species transcriptome atlas of mammalian embryogenesis delineates metabolic regulation across three different implantation modes
Mammalian embryogenesis relies on glycolysis and oxidative phosphorylation, but understanding of the dynamics of metabolic regulation in the postimplantation embryo in vivo remains elusive. Here the authors compile single-cell embryo profiling data in six mammalian species and reveal a conserved metabolic programme despite different implantation modes.
- Anna Malkowska
- , Christopher Penfold
- & Thorsten E. Boroviak
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| Open Access
Mechanical forces couple bone matrix mineralization with inhibition of angiogenesis to limit adolescent bone growth
The study shows that mechanical forces trigger secretion of the extracellular matrix protein dentin matrix protein 1 from osteoblasts. This transforms bone growth-promoting blood vessels into a quiescent subtype to limit bone growth at the end of adolescence.
- Maria Dzamukova
- , Tobias M. Brunner
- & Max Löhning
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ERK1/2 is an ancestral organising signal in spiral cleavage
How invertebrates with spiral cleavage establish their body plans is unclear. Here the authors show that, like molluscs, a basal annelid uses ERK1/2 to instruct body patterning, suggesting that this is a deep ancestral trait in animal embryogenesis.
- Océane Seudre
- , Allan M. Carrillo-Baltodano
- & José M. Martín-Durán
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Mesenchymal-epithelial crosstalk shapes intestinal regionalisation via Wnt and Shh signalling
The small intestine forms via crosstalk between epithelial and mesenchymal cell compartments. Here, the authors show that a gradient of Wnt signalling along the anterior-posterior axis regulates Sonic Hedgehog which is required for correct formation and regionalization of the small intestine.
- Martti Maimets
- , Marianne Terndrup Pedersen
- & Kim B. Jensen
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| Open Access
Type-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta
Collagen is the most abundant protein in the human body. Here, the authors show that different classes of fibroblasts produce collagen of unique functions with different impacts on embryo development and bone formation.
- Yang Chen
- , Sujuan Yang
- & Raghu Kalluri
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| Open Access
Repression of germline genes by PRC1.6 and SETDB1 in the early embryo precedes DNA methylation-mediated silencing
Germline genes are repressed by DNA methylation and histone marks. Here, the authors show that specific germline genes hypomethylated pre-implantation are enriched for PRC1.6, H2AK119ub1 and H3K9me3, which coordinately repress their expression.
- Kentaro Mochizuki
- , Jafar Sharif
- & Matthew C. Lorincz
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Single cell multi-omic analysis identifies a Tbx1-dependent multilineage primed population in murine cardiopharyngeal mesoderm
Perturbations of the cardiopharyngeal mesoderm can lead to congenital defects in individuals with 22q11.2 deletion syndrome. Here the authors use single cell RNA-sequencing to identify a multilineage primed population within the mesoderm, marked by Tbx1, which has bipotent properties to form cardiac and branchiomeric muscle cells.
- Hiroko Nomaru
- , Yang Liu
- & Bernice E. Morrow
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| Open Access
Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis
Activation of the zygotic genome is a critical transition during development, though the link to tissue-specific gene regulation remains unclear. Here the authors demonstrate distinct functions for Satb2 before and after zygotic genome activation, highlighting the temporal coordination of these roles.
- Saurabh J. Pradhan
- , Puli Chandramouli Reddy
- & Sanjeev Galande
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Article
| Open Access
A TALE/HOX code unlocks WNT signalling response towards paraxial mesoderm
Cells in the developing embryo interpret WNT signalling with context-dependence, but the mechanism decoding these cues is unclear. Here, the authors show that combinatorial TALE/HOX activity destabilizes nucleosomes at WNT-responsive regions to activate paraxial mesodermal genes.
- Luca Mariani
- , Xiaogang Guo
- & Elisabetta Ferretti
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| Open Access
Coordination of endothelial cell positioning and fate specification by the epicardium
It remains unclear how spatial information controls endothelial cell identity and behavior in the developing heart. Here the authors perform single cell RNA sequencing at key developmental timepoints in mice to interrogate cellular contributions to coronary vessel patterning and maturation in the epicardium.
- Pearl Quijada
- , Michael A. Trembley
- & Eric M. Small
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Article
| Open Access
Blood and lymphatic systems are segregated by the FLCN tumor suppressor
Blood and lymphatic vessels bear a strong resemblance but do not share a lumen, thus maintaining their distinct functions. Here, the authors describe that Folliculin, a tumor suppressor, prevents the fusion of these vessels during development by limiting the plasticity of venous and lymphatic endothelial cells.
- Ikue Tai-Nagara
- , Yukiko Hasumi
- & Yoshiaki Kubota
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| Open Access
Single-cell transcriptomics identifies divergent developmental lineage trajectories during human pituitary development
Editor’s summary_NCOMMS-19-41732B The anterior pituitary gland controls body growth and reproduction but how early development is dynamically regulated is unclear. Here, the authors use scRNA-seq of human fetal pituitaries to identify different developmental routes and state transitions of five hormone-producing cell lineages, and a hybrid epithelial/mesenchymal state of pituitary stem cells.
- Shu Zhang
- , Yueli Cui
- & Jie Qiao
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Article
| Open Access
Developmental potential of aneuploid human embryos cultured beyond implantation
Aneuploidy, abnormal chromosome number, is a major cause of early pregnancy loss. Here the authors determine the extent of post-implantation development of human embryos with common aneuploidies in culture, finding developmental arrest of monosomy 21 embryos, and trophoblast hypo-proliferation in trisomy 16 embryos.
- Marta N. Shahbazi
- , Tianren Wang
- & Magdalena Zernicka-Goetz
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| Open Access
Single-cell transcriptomic analysis identifies the conversion of zebrafish Etv2-deficient vascular progenitors into skeletal muscle
The signals restricting specification of vascular progenitors are unclear. Here, the authors use scRNAseq to identify transitional steps during blood and vascular development in zebrafish and identify Etv2 as repressing skeletal muscle differentiation in vascular progenitors.
- Brendan Chestnut
- , Satish Casie Chetty
- & Saulius Sumanas
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| Open Access
β-Catenin and FGFR2 regulate postnatal rosette-based adrenocortical morphogenesis
Multicellular rosettes are known to mediate complex cellular reorganization such as epithelial folding and branching during embryonal organogenesis. Here the authors show that rosette formation regulated by β-Catenin and FGFR2 mediate postnatal adrenal cortex zona glomerulosa morphogenesis.
- Sining Leng
- , Emanuele Pignatti
- & David T. Breault
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Article
| Open Access
Multi-level and lineage-specific interactomes of the Hox transcription factor Ubx contribute to its functional specificity
Many transcription factors regulate gene expression in a lineage- and process-specific manner, despite being expressed in several cell types. Here, the authors show that the Hox transcription factor Ubx has lineage-specific interactomes, which contribute to its cell context-dependent functions.
- Julie Carnesecchi
- , Gianluca Sigismondo
- & Ingrid Lohmann
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| Open Access
Anti-angiogenic effects of VEGF stimulation on endothelium deficient in phosphoinositide recycling
Tumors can overproduce pro-angiogenic ligands overcoming currently approved anti-angiogenic therapies and hindering their success. Here, the authors show that targeting phosphoinositide recycling during tumor angiogenesis harnesses the tumor’s own production of angiogenic ligands to deplete adjacent endothelial cells of the capacity to respond to these signals.
- Amber N. Stratman
- , Olivia M. Farrelly
- & Brant M. Weinstein
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| Open Access
The in vivo genetic program of murine primordial lung epithelial progenitors
The identity of the earliest murine in vivo lung epithelial progenitors (marked by NKX2-1 expression) is unclear. Here, the authors use single-cell RNA sequencing to define the genetic program of these lung primordial progenitors, which will improve in vitro lung specification of pluripotent stem cells.
- Laertis Ikonomou
- , Michael J. Herriges
- & Darrell N. Kotton
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| Open Access
Embryonic mesothelial-derived hepatic lineage of quiescent and heterogenous scar-orchestrating cells defined but suppressed by WT1
Activated hepatic stellate cells of putative mesodermal origin orchestrate scarring during injury. Here, the authors define a discrete morphologically plastic lineage of embryonic mesothelial-derived scar-orchestrating cells, through a distinct quiescent adult precursor, defined and paradoxically inhibited by WT1.
- Timothy James Kendall
- , Catherine Mary Duff
- & Nicholas Dixon Hastie
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Article
| Open Access
A conserved regulatory program initiates lateral plate mesoderm emergence across chordates
Numerous tissues are derived from the lateral plate mesoderm (LPM) but how this is specified is unclear. Here, the authors identify a pan-LPM reporter activity found in the zebrafish draculin (drl) gene that also shows transgenic activity in LPM-corresponding territories of several chordates, including chicken, axolotl, lamprey, Ciona, and amphioxus.
- Karin D. Prummel
- , Christopher Hess
- & Christian Mosimann
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Article
| Open Access
Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium
HSCs emerge from haemogenic endothelium (HE) in the dorsal aorta but whether these tissues share a common lineage is unclear. Here, the authors use a zebrafish runx1 reporter to show that HE maintains an arterial gene expression profile in the absence of Runx1, suggesting the aortic endothelium as a precursor of HE.
- Florian Bonkhofer
- , Rossella Rispoli
- & Roger Patient
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Article
| Open Access
Primary cilia regulate hematopoietic stem and progenitor cell specification through Notch signaling in zebrafish
Haematopoietic stem and progenitor cells (HSPCs) produce all blood lineages and arise from the haemogenic endothelium (HE) during embryogenesis. Here the authors show that genes specific to cilia formation are required for HSPC development in the HE in zebrafish through transduction of Notch signal.
- Zhibin Liu
- , Haiqing Tu
- & Feng Liu
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| Open Access
Implantation initiation of self-assembled embryo-like structures generated using three types of mouse blastocyst-derived stem cells
The precise cellular patterning and decisions of early embryogenesis have been hard to mimic in vitro. Here, the authors culture murine embryonic and trophoblast stem cells together with extra-embryonic endoderm stem cells to form embryo-like structures (ETX-embryoids), which can initiate an implantation response.
- Shaopeng Zhang
- , Tianzhi Chen
- & Jianyong Han
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Article
| Open Access
Venous identity requires BMP signalling through ALK3
The establishment of functional vasculatures requires the specification of newly formed vessels into veins and arteries. Here, Neal et al. use a combination of genetic approaches in mice and zebrafish to show that BMP signalling, via ALK3 and SMAD1/5, is required for venous specification during blood vessel development.
- Alice Neal
- , Svanhild Nornes
- & Sarah De Val
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| Open Access
Discoidin-domain receptor coordinates cell-matrix adhesion and collective polarity in migratory cardiopharyngeal progenitors
In Ciona, cardiopharyngeal progenitors migrate as polarized pairs of cells between the epidermis and the endoderm. Here the authors show that the endoderm secretes a particular collagen, which promotes Discoidin domain receptor activity to control cell-matrix adhesion and collective polarity.
- Yelena Y. Bernadskaya
- , Saahil Brahmbhatt
- & Lionel Christiaen
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| Open Access
Blood flow-induced Notch activation and endothelial migration enable vascular remodeling in zebrafish embryos
The mechanisms of sensing of blood flow and responses to it in vascular remodelling are poorly understood. Here, the authors show that in zebrafish blood flow controls both the fate determination of individual blood vessels and the arterial versus venous identity of endothelial cells lining them.
- Bart Weijts
- , Edgar Gutierrez
- & Eugene Tkachenko
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Article
| Open Access
Dynamic 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 Access
Loss 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
An amphioxus neurula stage cell atlas supports a complex scenario for the emergence of vertebrate head mesoderm