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| Open AccessSevere drought exposure in utero associates to children’s epigenetic age acceleration in a global climate change hot spot
The study suggests a positive association between in utero drought exposure and faster biological aging in children in a global climate change hot spot. Drought experienced during pregnancy may reduce life expectancy.
- Xi Qiao
- , Bilinda Straight
- & Belinda L. Needham
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Article
| Open AccessFOXC1 regulates endothelial CD98 (LAT1/4F2hc) expression in retinal angiogenesis and blood-retina barrier formation
FOXC1 transcription factor plays a role in vascular development, but its mechanism is not well defined. Here, the authors show FOXC1 regulates retinal angiogenesis by promoting CD98 amino acid transporter expression to activate mTOR signalling, and also by promoting blood-retina barrier formation.
- Teena Bhakuni
- , Pieter R. Norden
- & Tsutomu Kume
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Article
| Open AccessJag1/2 maintain esophageal homeostasis and suppress foregut tumorigenesis by restricting the basal progenitor cell pool
Dysregulation of basal progenitor cells induces esophageal tumorigenesis but the underlying mechanism is less explored. Here, the authors show that Jag1/2 deficiency promotes expansion of basal progenitor cells, leading to reduced squamous epithelial differentiation and enhanced formation of squamous cell carcinoma in the foregut.
- Haidi Huang
- , Yu Jiang
- & Yongchun Zhang
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Article
| Open AccessThree stepwise pH progressions in stratum corneum for homeostatic maintenance of the skin
Previous studies of the skin have suggested a neutral-to-acidic pH gradient in the outermost layer. Here, the authors perform quantitative intravital pH imaging of the stratum corneum, the outermost epidermal layer, and demonstrate three distinct pH zones - rather than a gradient - with different biological functions.
- Keitaro Fukuda
- , Yoshihiro Ito
- & Masayuki Amagai
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Article
| Open AccessProteostatic 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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Article
| Open AccessThree-dimensional liquid metal-based neuro-interfaces for human hippocampal organoids
Providing a suitable multi-electrode array (MEA) for free-floating neural organoids is a great challenge. Here, authors present a mesh soft stretchable MEA for recording neural signals in human hippocampal organoids derived from induced pluripotent stem cells.
- Yan Wu
- , Jinhao Cheng
- & Xingyu Jiang
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Article
| Open AccessCoordinated wound responses in a regenerative animal-algal holobiont
The term ‘holobiont’ refers to a multicellular organism and its microbial symbionts. Whether and how symbionts react to host injury and how cellular responses are integrated across species remain unexplored. Here, the authors report a deeply conserved animal regeneration regulatory program that links molecular networks across species in an animal-algal holobiont.
- Dania Nanes Sarfati
- , Yuan Xue
- & Bo Wang
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Article
| Open AccessDynamic microvilli sculpt bristles at nanometric scale
Bristleworms possess dedicated cells that can synthesize highly stereotypical bristles with sub-micrometric precision. Here, Ikeda and colleagues shed light on the underlying dynamics of cellular protrusions, revealing an extension-disassembly cycle that resembles a 3D printer.
- Kyojiro N. Ikeda
- , Ilya Belevich
- & Florian Raible
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Article
| Open AccessThe greenbeard gene tgrB1 regulates altruism and cheating in Dictyostelium discoideum
Greenbeards encode perceptible signals, signal recognition ability, and altruism towards others displaying the signal. This study shows that activation of the greenbeard receptor gene tgrB1 increases altruism and inactivation causes kin-specific cheating in the social amoeba Dictyostelium discoideum.
- Mariko Katoh-Kurasawa
- , Peter Lehmann
- & Gad Shaulsky
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Article
| Open AccessRegulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression
MYC regulates numerous genes involved in cell growth and proliferation. Here, Li-Bao et al. study the DNA regions that regulate Myc transcription in early mouse embryos and pluripotent stem cells. They report a specific region with independent modules dedicated to discrete temporal and spatial phases of Myc expression.
- Lin Li-Bao
- , Covadonga Díaz-Díaz
- & Miguel Torres
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Article
| Open AccessFused in sarcoma (FUS) inhibits milk production efficiency in mammals
Efficient milk production in mammals confers advantages by facilitating the transmission of energy from mother to offspring. However, the factors for establishing the efficiency in mammals are unknown. Here, the authors identify FUS as a regulator of efficient milk production in mammals.
- Haili Shao
- , Jipeng Huang
- & Baowei Jiao
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Article
| Open AccessTFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia
The role of coagulation system in erythropoiesis is not clear. Here, the authors report that an anticoagulant protein TFPI from erythroblasts directs central macrophages to synthesize heme, which in turn promotes erythropoiesis in bone marrow.
- Jun-Kai Ma
- , Li-Da Su
- & Xin-Jiang Lu
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Article
| Open AccessImplication of thermal signaling in neuronal differentiation revealed by manipulation and measurement of intracellular temperature
The role of subcellular thermogenesis during neuronal differentiation remains poorly understood. Here, the authors employ methods to monitor local intracellular temperature, and they investigate the effects of non-invasive temperature changes on cell differentiation using neuron-like cells.
- Shunsuke Chuma
- , Kazuyuki Kiyosue
- & Yoshie Harada
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Article
| Open AccessComplete male-to-female sex reversal in XY mice lacking the miR-17~92 cluster
The cluster miR-17~92 modulates the expression of genes networks and signalling pathways to ensure proper Sry expression timing and subsequent testis differentiation, an unexpected role for miRNAs in the early steps of mammalian sex determination.
- Alicia Hurtado
- , Irene Mota-Gómez
- & Francisco J. Barrionuevo
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Article
| Open AccessThe miR-144/Hmgn2 regulatory axis orchestrates chromatin organization during erythropoiesis
Differentiation of stem and progenitor cells is a highly regulated process. Here, the authors uncover miR-144 and its target Hmgn2 as the backbone of the genetic regulatory circuit that controls the terminal differentiation of erythrocytes in vertebrates.
- Dmitry A. Kretov
- , Leighton Folkes
- & Daniel Cifuentes
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Article
| Open AccessSpatially revealed roles for lncRNAs in Drosophila spermatogenesis, Y chromosome function and evolution
In Drosophila, long noncoding RNAs (lncRNAs) are expressed most highly in male germline cells. Here the authors report the subcellular distributions of approximately 600 Drosophila lncRNAs in male reproductive tissues, indicating potential involvement in spermatogenesis, fertility and evolution.
- Zhantao Shao
- , Jack Hu
- & Henry M. Krause
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Article
| Open AccessA human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations
Copy number alterations in stem cells impair neural crest differentiation and set the stage for neuroblastoma-like traits and tumours. This study hints at early tumourigenesis mechanisms and finds developmental gene signatures linked to prognosis.
- Ingrid M. Saldana-Guerrero
- , Luis F. Montano-Gutierrez
- & Florian Halbritter
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Article
| Open AccessPrimordial germ cell DNA demethylation and development require DNA translesion synthesis
Here the authors show that DNA translesion synthesis affects primordial germ cell DNA demethylation and plays a role in the development of embryonic germ cells.
- Pranay Shah
- , Ross Hill
- & Gerry P. Crossan
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Article
| Open AccessAcinar to β-like cell conversion through inhibition of focal adhesion kinase
A cure for diabetes could entail an effective cell replacement therapy through generation of new insulinproducing cells. In this study, we show that inhibition of focal adhesion kinase activity results in transdifferentiation of a subset of peri-islet acinar cells into functional insulin producing β-like cells.
- Shakti Dahiya
- , Mohamed Saleh
- & Farzad Esni
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Article
| Open AccessAtypical heat shock transcription factor HSF5 is critical for male meiotic prophase under non-stress conditions
The regulation of meiotic prophase progression varies between males and females. This study reveals the involvement of an atypical heat shock transcription factor HSF5 in gene expression during male meiotic prophase and highlights the involved gene regulatory mechanism.
- Saori Yoshimura
- , Ryuki Shimada
- & Kei-ichiro Ishiguro
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Article
| Open AccessAntigen presentation plays positive roles in the regenerative response to cardiac injury in zebrafish
An adequate immune response is necessary to promote heart regeneration. Here, the authors identified a link between antigen presentation, immune cells, and endocardial cells during the regenerative response to cardiac injury in the adult zebrafish.
- João Cardeira-da-Silva
- , Qianchen Wang
- & Didier Y. R. Stainier
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Article
| Open AccessSkin graft with dermis and appendages generated in vivo by cell competition
Skin substitutes generated by tissue engineering have limited properties. Here, authors established niche encroachment method. Cell competition enabled skin organogenesis from allogeneic and xenogeneic stem cells on p63 knockout embryos, resulting in a complete skin graft on dermis with hair.
- Hisato Nagano
- , Naoaki Mizuno
- & Hiromitsu Nakauchi
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Article
| Open AccessA MTA2-SATB2 chromatin complex restrains colonic plasticity toward small intestine by retaining HNF4A at colonic chromatin
The large intestine mucosa possesses a surprising plasticity to switch on small intestine genes. Here, Wei G. et al. show that a chromatin complex composed of SATB2, MTA2 and HNF4A regulates this tissue plasticity in the adult gut.
- Wei Gu
- , Xiaofeng Huang
- & Qiao Zhou
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Article
| Open AccessDiphthamide deficiency promotes association of eEF2 with p53 to induce p21 expression and neural crest defects
Rare disease DEDSSH1-associated DPH1 mutations impair eEF2 diphthamide modification that leads to eEF2 as a transcriptional coactivator for p53 to enhance expression of the cell proliferation inhibitor p21, resulting in birth defects.
- Yu Shi
- , Daochao Huang
- & Weihong Song
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Article
| Open AccessSingle-cell analyses reveal transient retinal progenitor cells in the ciliary margin of developing human retina
Formation of the retina during development involves the coordinated action of retinal progenitor cells and their differentiated cell types, which is key for producing a functioning eye. Here the authors provide a detailed atlas of human retinal development, combining scRNA-seq and spatial transcriptomics, and identify key genetic factors that mediate retinal progenitor cell proliferation and differentiation.
- Birthe Dorgau
- , Joseph Collin
- & Majlinda Lako
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Article
| Open AccessNumb positively regulates Hedgehog signaling at the ciliary pocket
The precise regulatory mechanisms controlling ciliary Hedgehog signaling remain incomplete. Here, the authors use ciliary proteomics to reveal that Numb facilitates the endocytosis of the receptor Ptch1 from the ciliary pocket, thereby enabling activation of Hedgehog signaling.
- Xiaoliang Liu
- , Patricia T. Yam
- & Xuecai Ge
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Article
| Open Accesshoxc12/c13 as key regulators for rebooting the developmental program in Xenopus limb regeneration
During organ regeneration, gene expression patterns similar to those in normal development are reestablished. Here, Kawasumi-Kita et al. explore core rebooting factors that operate during Xenopus limb regeneration. Their results indicate that hoxc12 and hoxc13 are critical for reactivating tissue growth.
- Aiko Kawasumi-Kita
- , Sang-Woo Lee
- & Yoshihiro Morishita
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Article
| Open AccessLSD1 drives intestinal epithelial maturation and controls small intestinal immune cell composition independent of microbiota in a murine model
Post birth the gastrointestinal tract undergoes development including the establishment of the microbiome, establishment of tolerance and maturation of the epithelium. Here the authors show a histone demethylase LSD1 is required for postnatal intestinal epithelium maturation and how this impacts local immune cell composition and gut homeostasis.
- Alberto Díez-Sánchez
- , Håvard T. Lindholm
- & Menno J. Oudhoff
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Comment
| Open AccessInflammation and mitophagy are mitochondrial checkpoints to aging
Cellular and organismal aging have been consistently associated with mitochondrial dysfunction and inflammation. Accumulating evidence indicates that aging-related inflammatory responses are mechanistically linked to compromised mitochondrial integrity coupled with mtDNA-driven CGAS activation, a process that is tonically inhibited by mitophagy.
- Emma Guilbaud
- , Kristopher A. Sarosiek
- & Lorenzo Galluzzi
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Article
| Open AccessLKRSDH-dependent histone modifications of insulin-like peptide sites contribute to age-related circadian rhythm changes
Age has an impact on circadian rhythm. Here, the authors report that LKRSDH-dependent H3R17me2 and H3K27me3 at insulin-like peptide sites contribute to age-related circadian rhythm change in Drosophila.
- Pengfei Lv
- , Xingzhuo Yang
- & Juan Du
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Article
| Open AccessCdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila
Mitochondrial fission, performed by Drp1, is carefully regulated, particularly in neurons. Here, the authors examine Drosophila Cdk8/CDK19 function in mitochondrial fission and uncover a role phosphorylating Drp1 in the cytoplasm and show overexpression suppresses a Parkinson’s disease model.
- Jenny Zhe Liao
- , Hyung-lok Chung
- & Esther M. Verheyen
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Article
| Open AccessPhysiological DNA damage promotes functional endoreplication of mammary gland alveolar cells during lactation
Breastfeeding confers lifelong benefits to both mother and child, yet women worldwide experience lactation insufficiency. Here, the authors show that DNA damage occurring in the breast during pregnancy drives the generation of milk-producing cells.
- Rut Molinuevo
- , Julien Menendez
- & Lindsay Hinck
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Article
| Open AccessCombined and differential roles of ADD domains of DNMT3A and DNMT3L on DNA methylation landscapes in mouse germ cells
DNMT3A and DNMT3L form a complex to deposit DNA methylation in mammalian germ cells. Here, the authors report that loss-of-function of ADD domains of DNMT3A and/or DNMT3L has various impacts on DNA methylation landscapes in mouse oocytes and sperm.
- Naoki Kubo
- , Ryuji Uehara
- & Hiroyuki Sasaki
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Article
| Open AccessAnnelid adult cell type diversity and their pluripotent cellular origins
The cellular atlas of Pristina leidyi reveals cell type diversity in adult annelids by single cell transcriptomics, discovering several novel cell types and suggesting a pluripotent stem cell signature associated with adult cell type differentiation
- Patricia Álvarez-Campos
- , Helena García-Castro
- & Jordi Solana
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Article
| Open AccessDynamic interplay of microtubule and actomyosin forces drive tissue extension
Actomyosin and microtubule-based forces are both important for tissue development, but how these systems interact in space and time remains unclear. Here, the authors study fly wing epithelium growth and determine aspects driving cell shape that are driven by microtubule or actomyosin-generated forces.
- Amrita Singh
- , Sameedha Thale
- & Maja Matis
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Article
| Open AccessDeficiency of the HGF/Met pathway leads to thyroid dysgenesis by impeding late thyroid expansion
The mechanisms of bifurgation, a key step in thyroid development, are largely unknown. Here, Fang et al. find that HGF/Met is indispensable for the bifurgation of the thyroid primordium during zebrafish thyroid development.
- Ya Fang
- , Jia-Ping Wan
- & Huai-Dong Song
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Article
| Open AccessParenchymal 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 AccessCell-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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Article
| Open AccessDecoding spatiotemporal transcriptional dynamics and epithelial fibroblast crosstalk during gastroesophageal junction development through single cell analysis
Elucidating the gastroesophageal junction’s development is key to comprehending its disease susceptibility. Here, the authors mapped its development, uncovering cellular diversity and interaction dynamics using advanced spatiotemporal single-cell analysis.
- Naveen Kumar
- , Pon Ganish Prakash
- & Cindrilla Chumduri
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Article
| Open AccessDHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells
Inflammatory bowel disease (IBD) is featured with epithelial barrier dysfunction, however, the underlying mechanism is less clear. Here, the authors show that DHX9 deficiency in intestinal stem cells (ISCs) induces accumulation of abnormal R-loops and subsequent genomic instability, leading to impairment of ISCs and development of IBD.
- Xingxing Ren
- , Qiuyuan Liu
- & Shu Zhu
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Article
| Open AccessBasal actomyosin pulses expand epithelium coordinating cell flattening and tissue elongation
Actomyosin networks constrict cell area and junctions to alter cell and tissue shape. Here, Li et al. reveal a morphological cell expansion wave behaviour that coordinates epithelial flattening and tissue elongation during Drosophila oogenesis.
- Shun Li
- , Zong-Yuan Liu
- & Xiaobo Wang
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Article
| Open AccessCis-regulatory interfaces reveal the molecular mechanisms underlying the notochord gene regulatory network of Ciona
The notochord is an essential hallmark of the chordate phylum. Here, Negrón-Piñeiro et al. study the notochord gene regulatory network in Ciona, and their findings illustrate how notochord transcription factors are coordinated by Brachyury and Foxa2.
- Lenny J. Negrón-Piñeiro
- , Yushi Wu
- & Anna Di Gregorio
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Article
| Open AccessSystematic HOIP interactome profiling reveals critical roles of linear ubiquitination in tissue homeostasis
Authors perform an in vivo mass spectrometry-based interactome analysis of HOIL-1-interacting protein, a key component of linear ubiquitination assembly complex.
- Yesheng Fu
- , Lei Li
- & Lingqiang Zhang
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Article
| Open AccessPaternal dietary macronutrient balance and energy intake drive metabolic and behavioral differences among offspring
The dietary factors causing varying intergenerational responses are not fully identified. Here, the authors show that the relative proportion of protein, fats, and carbohydrates in paternal diets before conception differentially influences the phenotype of the next-generation offspring on energy metabolism and behaviour.
- Angela Jane Crean
- , Alistair McNair Senior
- & Stephen James Simpson
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Article
| Open AccessDifferentiation granules, a dynamic regulator of T. brucei development
The African trypanosome Trypanosoma brucei has been shown to form stress granules in vitro that might be repurposed to enable differentiation and facilitate parasite transmission. Here, Cayla et al. show that differentiation between slender and stumpy forms does involve membrane-less granules that are different from nutritional stress granules.
- Mathieu Cayla
- , Christos Spanos
- & Keith R. Matthews
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Article
| Open AccessCompensatory growth and recovery of cartilage cytoarchitecture after transient cell death in fetal mouse limbs
How growing organs recover from transient injuries is unclear. Here, authors used mouse models of transient cell death in the limb cartilage to identify cellular and molecular mechanisms (e.g. mTORC1) involved in cartilage repair and catch-up growth.
- Chee Ho H’ng
- , Shanika L. Amarasinghe
- & Alberto Rosello-Diez
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Article
| Open AccessSOXC are critical regulators of adult bone mass
Angelozzi et al. uncover key mechanisms involved in physiological and pathological bone mass remodeling by showing that SOXC transcription factors regulate the bone formation and resorption balance via critical roles in LepR+ mesenchymal stem cells.
- Marco Angelozzi
- , Anirudha Karvande
- & Véronique Lefebvre
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Article
| Open AccessTwo orthogonal differentiation gradients locally coordinate fruit morphogenesis
The coordination of cellular behaviors is essential for proper organogenesis. Here the authors show that fruit development in Arabidopsis is governed by time-shifted differentiation gradients that act locally along two perpendicular organ axes.
- Andrea Gómez-Felipe
- , Elvis Branchini
- & Daniel Kierzkowski
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Article
| Open AccessEph-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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