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Article
| Open Access
Ripply suppresses Tbx6 to induce dynamic-to-static conversion in somite segmentation
During somitogenesis, the dynamic oscillation of the molecular clock is converted into static spatial patterns. Here, the authors show that persistent suppression of Tbx6 expression triggered by periodical Ripply1/2 gene expression is a key to this conversion.
- Taijiro Yabe
- , Koichiro Uriu
- & Shinji Takada
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Article
| Open Access
Membrane potential drives the exit from pluripotency and cell fate commitment via calcium and mTOR
The plasma membrane’s electrical potential is maintained by ion channels, though the impact of this potential on cell fate has not been clearly elucidated. Here they show that changes in membrane potential can affect calcium levels and mTOR in pluripotent stem cells, altering their transition from pluripotency to differentiation.
- Emily Sempou
- , Valentyna Kostiuk
- & Mustafa K. Khokha
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| Open Access
A stem cell roadmap of ribosome heterogeneity reveals a function for RPL10A in mesoderm production
How ribosomes differ in composition and function to regulate gene expression is poorly understood. Here, the authors show that ribosome composition changes during stem cell differentiation and identify a ribosomal protein that regulates production of the mesoderm lineage.
- Naomi R. Genuth
- , Zhen Shi
- & Maria Barna
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Article
| Open Access
Spatial regulation by multiple Gremlin1 enhancers provides digit development with cis-regulatory robustness and evolutionary plasticity
The BMP antagonist Gremlin1 balances BMP and SHH signalling, endowing limb bud development with robustness. Here, the authors identify enhancers controlling Grem1 levels in an additive, and spatial regulation in a synergistic manner, providing digit patterning with cis-regulatory robustness and evolutionary plasticity.
- Jonas Malkmus
- , Laurène Ramos Martins
- & Rolf Zeller
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Article
| Open Access
Identification of limb-specific Lmx1b auto-regulatory modules with Nail-patella syndrome pathogenicity
Nail-patella syndrome (NPS) is characterized by nail dysplasia, absent/hypoplastic patellae, chronic kidney disease, and glaucoma and can be caused by haploinsufficiency of LMX1B; however, not all patients harbor pathogenic LMX1B mutations. Here the authors show that loss-of-function variations in upstream enhancer sequences are responsible for a limb specific form of human NPS.
- Endika Haro
- , Florence Petit
- & Kerby C. Oberg
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Article
| Open Access
Amnion signals are essential for mesoderm formation in primates
Human and murine embryonic development has disparities, highlighting the need for primate systems. Here, the authors construct a post-implantation transcriptional atlas from non-human primate embryos and show ISL1 controls a gene regulatory network in the amnion required for mesoderm formation.
- Ran Yang
- , Alexander Goedel
- & Kenneth R. Chien
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Article
| Open Access
Fibroblast fusion to the muscle fiber regulates myotendinous junction formation
Classically, myogenic precursor cells derive from somites, and connective tissues derive from lateral plate mesoderm (LPM). Here the authors identify LPM derived fibroblasts that turn on a myogenic program and fuse to muscle fibers at muscle-tendon junctions, introducing fibroblast transcripts into myofibers.
- Wesal Yaseen
- , Ortal Kraft-Sheleg
- & Peleg Hasson
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| Open Access
In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche
Short term systemic expression of the reprogramming factors Oct-3/4, Sox2, Klf4, c-Myc (OSKM) rejuvenates aging cells and promotes tissue regeneration. Here the authors show that myofiber-specific expression of OSKM accelerates muscle regeneration by reducing secretion of muscle stem cell quiescence promoting Wnt4.
- Chao Wang
- , Ruben Rabadan Ros
- & Juan Carlos Izpisua Belmonte
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| Open Access
Mechanical impact of epithelial−mesenchymal transition on epithelial morphogenesis in Drosophila
Tissue folding is a critical process during developmental morphogenesis. Here, Gracia et al. use live imaging, laser ablation and in silico modelling to demonstrate that cells entering EMT generate orthogonal forces necessary to drive mesoderm invagination in Drosophila.
- Mélanie Gracia
- , Sophie Theis
- & Magali Suzanne
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| Open Access
Pervasive translational regulation of the cell signalling circuitry underlies mammalian development
Gene expression is regulated at several levels, including through the modulation of protein translation. Here the authors find that translation control diversifies gene expression between developing tissues and regulates major signalling pathways through a complex landscape of upstream open reading frames (uORFs).
- Kotaro Fujii
- , Zhen Shi
- & Maria Barna
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| Open Access
Bulk cell density and Wnt/TGFbeta signalling regulate mesendodermal patterning of human pluripotent stem cells
Differentiation of human pluripotent stem cells (hPSC) mimics aspects of embryonic developmentin vitrobut is poorly understood. Here, the authors identify bulk cell density as a key parameter directing transition from pluripotency to primitive streak-like priming in hPSCs via secreted LEFTY/CERBERUS.
- Henning Kempf
- , Ruth Olmer
- & Robert Zweigerdt
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Article
| Open Access
BMP 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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HEB associates with PRC2 and SMAD2/3 to regulate developmental fates
In embryonic stem cells, extracellular signals are required to derepress developmental promoters to drive lineage specification, but the proteins involved in this process remain unknown. Here the authors show that the protein HEB directly associates with the Polycomb repressive complex 2 at genes involved in mesoderm and endoderm specification.
- Se-Jin Yoon
- , Joseph W. Foley
- & Julie C. Baker
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Primitive macrophages control HSPC mobilization and definitive haematopoiesis
Haematopoietic stem/progenitor cells (HSPCs) transform from aortic endothelium into migratory cells that move through stroma and enter circulation to colonize haematopoietic tissues. Here the authors show that HSPCs' passage is facilitated by primitive macrophages that secrete extracellular matrix-degrading enzymes.
- Jana Travnickova
- , Vanessa Tran Chau
- & Karima Kissa
Tgfbr1 controls developmental plasticity between the hindlimb and external genitalia by remodeling their regulatory landscape