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Article
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Parenchymal cues define Vegfa-driven venous angiogenesis by activating a sprouting competent venous endothelial subtype
Organs develop unique vascular architectures to support physiological functions. Here, authors show that organo-typical vascular networks may arise from specific parenchymal cues activating unique endothelial subtypes and angiogenic sprouting processes.
- Laetitia Préau
- , Anna Lischke
- & Ferdinand le Noble
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Article
| Open Access
The level of protein in the maternal murine diet modulates the facial appearance of the offspring via mTORC1 signaling
Children’s faces resemble their parents to various degrees. Here they show that the maternal diet affects the facial appearances of newborns and that inherited and adaptive mechanisms sculpturing facial bones are linked via dietary protein levels and the mTOR signaling pathway.
- Meng Xie
- , Markéta Kaiser
- & Andrei S. Chagin
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Article
| Open Access
Tgfbr1 controls developmental plasticity between the hindlimb and external genitalia by remodeling their regulatory landscape
Development of hindlimbs and external genitalia share several regulatory factors. Lozovska et al. show that Tgfbr1 controls the response to those factors; embryos lacking Tgfbr1 develop two sets of hindlimbs at the expense of the external genitalia.
- Anastasiia Lozovska
- , Artemis G. Korovesi
- & Moisés Mallo
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Article
| Open Access
Sea lamprey enlightens the origin of the coupling of retinoic acid signaling to vertebrate hindbrain segmentation
Retinoic acid signaling is involved in patterning the embryonic antero-posterior axis, and also regulates hindbrain segmentation in jawed vertebrates. Here they show that retinoic acid signaling plays important roles in hindbrain segmentation in a jawless vertebrate, the lamprey, thus indicating this feature of hindbrain development is conserved in all vertebrates.
- Alice M. H. Bedois
- , Hugo J. Parker
- & Robb Krumlauf
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Article
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Regulation of long-range BMP gradients and embryonic polarity by propagation of local calcium-firing activity
Identical twins from a single embryo are formed in multiple species, albeit rarely. It is not clear how such twinning is suppressed during early development. Here they show that calcium signalling activity is propagated through the extraembryonic tissue to prevent ectopic primitive streak formation during gastrulation.
- Hyung Chul Lee
- , Nidia M. M. Oliveira
- & Claudio D. Stern
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Article
| Open Access
Time-integrated BMP signaling determines fate in a stem cell model for early human development
The interpretation of the key developmental signal BMP remains poorly understood. Here, the authors show that the total time-integrated signaling controls differentiation in a stem cell embryo model and provide a possible mechanism.
- Seth Teague
- , Gillian Primavera
- & Idse Heemskerk
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Article
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R-Spondin 2 governs Xenopus left-right body axis formation by establishing an FGF signaling gradient
Left-right (LR) body asymmetry is established by leftward flow in the LR organizer. Here, the authors show in Xenopus that R-Spondin 2 acts as an FGF receptor antagonist that produces a right-to-left FGF signaling gradient in response to flow to break LR symmetry.
- Hyeyoon Lee
- , Celine Marie Camuto
- & Christof Niehrs
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Matters Arising
| Open Access
Reply to: Assessing the precision of morphogen gradients in neural tube development
- Roman Vetter
- & Dagmar Iber
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Article
| Open Access
Histone lactylation couples cellular metabolism with developmental gene regulatory networks
While metabolic reprogramming has been shown to drive changes in cell identity, the link between cellular metabolism and gene expression remains poorly characterized. Here they show that histone lactylation couples metabolism and transcription during neural crest cell differentiation in the early embryo.
- Fjodor Merkuri
- , Megan Rothstein
- & Marcos Simoes-Costa
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Article
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Role of UPF1-LIN28A interaction during early differentiation of pluripotent stem cells
UPF1 and LIN28A are RNA-binding proteins involved in post-transcriptional regulation and cell differentiation. Here, authors report that they interact with each other via specific domains and regulate ectodermal specialization of human pluripotent stem cells.
- Seungwon Jung
- , Seung Hwan Ko
- & Jungwook Hwang
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Article
| Open Access
Determining zebrafish dorsal organizer size by a negative feedback loop between canonical/non-canonical Wnts and Tlr4/NFκB
Dorsal organizer initiates the dorsal-ventral axis formation in vertebrates. Here, the authors demonstrate that Tlr4/NFκB-mediated negative feedback regulation of Wnt/β-catenin signaling determines the precise size of the zebrafish dorsal organizer.
- Juqi Zou
- , Satoshi Anai
- & Tohru Ishitani
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Article
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Stochastic gene expression and environmental stressors trigger variable somite segmentation phenotypes
Mutations of several genes cause variable phenotypes. Here, the authors show stochastic her1 and her7 gene expression, which is affected by environmental conditions, underlies variability of somite segmentation defects.
- Kemal Keseroglu
- , Oriana Q. H. Zinani
- & Ertuğrul M. Özbudak
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Article
| Open Access
The USP46 deubiquitylase complex increases Wingless/Wnt signaling strength by stabilizing Arrow/LRP6
Wnt receptor levels drive signaling. Here the authors find that precise signaling in the Wnt morphogen gradient relies on Usp46, a deubiquitylase that enhances target cells sensitivity by increasing cell surface levels of the Wnt receptor Arrow/LRP6.
- Zachary T. Spencer
- , Victoria H. Ng
- & Yashi Ahmed
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Article
| Open Access
Fgf signalling triggers an intrinsic mesodermal timer that determines the duration of limb patterning
The limb bud is patterned by crosstalk between the mesoderm and the overlying apical ectodermal ridge, but it has been difficult to determine the requirement for different ligands in this process. Here the authors use a chick wing explant system to show that fibroblast growth factors trigger a mesodermal programme that is key for timing limb bud patterning.
- Sofia Sedas Perez
- , Caitlin McQueen
- & Matthew Towers
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Article
| Open Access
Targeted mechanical stimulation via magnetic nanoparticles guides in vitro tissue development
Highly localized mechanical forces that shape in vivo tissue development remain challenging to recapitulate in vitro. Here the authors use magnetically actuated nanoparticles to generate spatially defined forces within organoids, which guide the spatial organization of tissue patterning and growth.
- Abdel Rahman Abdel Fattah
- , Niko Kolaitis
- & Adrian Ranga
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Article
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A BLADE-ON-PETIOLE orthologue regulates corolla differentiation in the proximal region in Torenia fournieri
Flowers manifest enormous diversity and shape is determined by morphogenesis along different independent axes. Here Su et al. report a shared BOP-ALOG module that regulates corolla differentiation in the proximal region axis.
- Shihao Su
- , Yawen Lei
- & Tetsuya Higashiyama
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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
Jag1-Notch cis-interaction determines cell fate segregation in pancreatic development
Notch signaling is crucial for pancreatic cell fate choice. With mathematical modeling and experiments, Xu et al. provides new insights into how different Notch ligands and Hes1 oscillation guide the spatial-temporal dynamics of cell differentiation.
- Xiaochan Xu
- , Philip Allan Seymour
- & Palle Serup
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Article
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Wnt/β-catenin signalling is required for pole-specific chromatin remodeling during planarian regeneration
Any planarian fragment regenerates the missing head and tail in the proper end. Early activation of the Wnt/β-catenin signaling pathway changes the chromatin accessibility of the cells of the posterior-facing wound to regenerate a tail.
- Eudald Pascual-Carreras
- , Marta Marín-Barba
- & Teresa Adell
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Article
| Open Access
TBX2 specifies and maintains inner hair and supporting cell fate in the Organ of Corti
Inner hair cells are essential for hearing but the molecular drivers of their differentiation have remained enigmatic. Here, the authors show that the transcription factor TBX2 has a key function in inducing and maintaining inner hair cell fate.
- Marina Kaiser
- , Timo H. Lüdtke
- & Mark-Oliver Trowe
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Article
| Open Access
Creb5 coordinates synovial joint formation with the genesis of articular cartilage
Zhang et al. show that the Creb5 transcription factor regulates the formation of synovial joints, directs the genesis of articular cartilage, and regulates the shape of the ends of long bones by blocking Wnt5a expression in the perichondrium.
- Cheng-Hai Zhang
- , Yao Gao
- & Andrew B. Lassar
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Article
| Open Access
Patterned mechanical feedback establishes a global myosin gradient
How does DNA encode shape? Here, via in toto light sheet microscopy and optogenetic control of cellular forces, the authors show that spatially patterned mechanical feedback loops establish the cytoskeletal patterns driving axis elongation tissue flow in Drosophila.
- Hannah J. Gustafson
- , Nikolas Claussen
- & Sebastian J. Streichan
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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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Article
| Open Access
A hierarchical transcription factor cascade regulates enteroendocrine cell diversity and plasticity in Drosophila
Here the authors elucidate a simple transcription factor code that underlies the complex genetic specification of enteroendocrine cell (EE) subtypes, and reveal significant cellular plasticity amongst EE subtypes.
- Xingting Guo
- , Yongchao Zhang
- & Rongwen Xi
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Article
| Open Access
Function of bidirectional sensitivity in the otolith organs established by transcription factor Emx2
The inner ear is highly organized, with distinct domains being located across the Line of Polarity Reversal (LPR). Here they show that Emx2 establishes the LPR and bidirectional selectivity of otolith organs, and that loss of the LPR in mice affects swimming and balance.
- Young Rae Ji
- , Yosuke Tona
- & Doris K. Wu
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Article
| Open Access
Single-molecule tracking of Nodal and Lefty in live zebrafish embryos supports hindered diffusion model
Multiple models have been proposed for how diffusion is regulated to shape morphogen gradients. Here they use single molecule tracking of an activator-inhibitor signaling pair in a developing tissue to show how effective diffusivity is modulated in the extracellular space.
- Timo Kuhn
- , Amit N. Landge
- & J. Christof M. Gebhardt
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Article
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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
Specificity of the Hox member Deformed is determined by transcription factor levels and binding site affinities
Despite the central role of Hox genes in controlling morphogenesis, the DNA binding of different Hox members is relatively similar. Here they show that specificity of Hox member Dfd relies on a precise balance of transcription factors and binding site affinities.
- Pedro B. Pinto
- , Katrin Domsch
- & Ingrid Lohmann
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Article
| Open Access
Maternal SMCHD1 regulates Hox gene expression and patterning in the mouse embryo
Parents transmit both genetic and epigenetic information to their offspring, with maternal effect genes being critical regulators of the offspring epigenome. Here they show that maternally deposited SMCHD1 has long-lasting effects on Hox gene expression and vertebral patterning during post-implantation development.
- Natalia Benetti
- , Quentin Gouil
- & Marnie E. Blewitt
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Article
| Open Access
Etv2 regulates enhancer chromatin status to initiate Shh expression in the limb bud
The embryonic limb bud is known to be patterned by a Shh morphogen gradient, though how Shh expression is activated remains less clear. Here the authors show that Etv2 acts as a pioneer transcription factor to mediate accessibility of the ZRS enhancer and initiate Shh expression.
- Naoko Koyano-Nakagawa
- , Wuming Gong
- & Daniel J. Garry
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Article
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HOX epimutations driven by maternal SMCHD1/LRIF1 haploinsufficiency trigger homeotic transformations in genetically wildtype offspring
Hox genes are known to control anteroposterior patterning, including the vertebrate spine. Here Xue et al. show that maternal Smchd1 regulates Hox expression in an epigenetic manner, and that wild type offspring from heterozygous mothers show skeletal homeotic transformations as a result of this dysregulation.
- Shifeng Xue
- , Thanh Thao Nguyen Ly
- & Bruno Reversade
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Article
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Single-cell chromatin profiling of the primitive gut tube reveals regulatory dynamics underlying lineage fate decisions
The primitive gut tube gives rise to all major internal organs, while underlying regulatory mechanisms are unclear. Here, the authors analyze its chromatin landscape at the single-cell level and define the epigenetic regulation of lineage fate decisions and plasticity in organ development and homeostasis.
- Ryan J. Smith
- , Hongpan Zhang
- & Tae-Hee Kim
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Article
| Open Access
Periodic formation of epithelial somites from human pluripotent stem cells
Somitogenesis has been well characterized in model organisms, resulting in detailed description of the somite segmentation clock. Here they generate somitogenic organoids from human pluripotent stem cells that recapitulate somitogenesis, periodic segmentation, and proper polarity.
- Marina Sanaki-Matsumiya
- , Mitsuhiro Matsuda
- & Miki Ebisuya
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Article
| Open Access
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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Article
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Tig1 regulates proximo-distal identity during salamander limb regeneration
The mechanisms by which cells determine their position within the 3D space are poorly understood. Research in salamanders offers fresh insights into this question, uncovering Tig1 as a central determinant of proximo-distal identity in regeneration.
- Catarina R. Oliveira
- , Dunja Knapp
- & Maximina H. Yun
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Article
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Precision of morphogen gradients in neural tube development
Morphogen gradients encode positional information during development. Here the authors use theory and simulations to suggest a positional accuracy of single gradients that directly explains the observed precision of progenitor domain boundaries.
- Roman Vetter
- & Dagmar Iber
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Article
| Open Access
Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids
Studying morphogen gradient formation and reception in mammalian development is challenging. Here, the authors show with human gastruloids that Nodal activity in live cells spreads via a relay mechanism with timing that is locally controlled by Lefty, which dictates mesoderm differentiation timing.
- Lizhong Liu
- , Anastasiia Nemashkalo
- & Aryeh Warmflash
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Article
| Open Access
Integration of single-cell transcriptomes and chromatin landscapes reveals regulatory programs driving pharyngeal organ development
The molecular basis and gene regulatory networks driving pharyngeal endoderm development remain poorly understood. Here the authors report single cell transcriptomic and chromatin landscapes to delineate regulatory programs driving this process and to define the immunodeficiency-associated developmental defects resulting from Foxn1 dysfunction.
- Margaret E. Magaletta
- , Macrina Lobo
- & René Maehr
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Article
| Open Access
Tissue fluidity mediated by adherens junction dynamics promotes planar cell polarity-driven ommatidial rotation
Ommatidial rotation in the Drosophila eye is a regulated process and a Planar Cell Polarity (PCP) cell motility model. Here, the authors show that tissue fluidity via junctional remodeling, as regulated by the PCP effector kinase Nemo, is critical for this cell motility process.
- Nabila Founounou
- , Reza Farhadifar
- & Marek Mlodzik
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Article
| Open Access
Self-organization of human dorsal-ventral forebrain structures by light induced SHH
Organizing centers act to pattern surrounding tissues during embryogenesis through the secretion of morphogens. Here the authors model human organizers using light stimulus to geometrically confine SHH expression in differentiating hESCs, generating spatially resolved proximal distal patterns.
- Riccardo De Santis
- , Fred Etoc
- & Ali H. Brivanlou
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Article
| Open Access
Asymmetric requirement of Dpp/BMP morphogen dispersal in the Drosophila wing disc
Morphogens disperse to pattern tissues and control their growth during development, allowing for the specification of multiple fates across space. Here the authors block dispersal of a morphogen Dpp (BMP2/4) and show that the requirement for Dpp dispersal is much lower than previously thought.
- Shinya Matsuda
- , Jonas V. Schaefer
- & Markus Affolter
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Article
| 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
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
Bicc1 and Dicer regulate left-right patterning through post-transcriptional control of the Nodal inhibitor Dand5
The authors show that post-transcriptional regulation of the cilia-driven leftward flow target dand5 is central to symmetry breakage in frog, fish and mouse and is mediated by a 139 nt Bicc1 responsive element in the dand5 3′UTR, and they present evidence that Pkd2 regulates this Bicc1/dand5 module.
- Markus Maerker
- , Maike Getwan
- & Axel Schweickert
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Article
| Open Access
Developmental genetics of color pattern establishment in cats
Intricate color patterns are a defining aspect of morphological diversity in the Felidae. Here the authors apply morphological and single-cell gene expression analysis to fetal skin of domestic cats to identify when, where, and how, during fetal development, felid color patterns are established.
- Christopher B. Kaelin
- , Kelly A. McGowan
- & Gregory S. Barsh
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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
Cnidarian-bilaterian comparison reveals the ancestral regulatory logic of the β-catenin dependent axial patterning
The authors show in Nematostella that the more orally expressed β-catenin targets repress the more aborally expressed β-catenin targets, thus patterning the oral-aboral axis. This likely represents the common mechanism of β-catenin-dependent axial patterning shared by Cnidaria and Bilateria.
- Tatiana Lebedeva
- , Andrew J. Aman
- & Grigory Genikhovich
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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
Diphthamide deficiency promotes association of eEF2 with p53 to induce p21 expression and neural crest defects