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Article
| Open AccessEndogenous clock-mediated regulation of intracellular oxygen dynamics is essential for diazotrophic growth of unicellular cyanobacteria
The authors investigate the circadian clock in a unicellular diazotrophic cyanobacterium. They demonstrate the role of the clock in regulating intracellular oxygen dynamics, a necessity to accommodate nitrogen fixation in an oxygen-producing cell.
- Anindita Bandyopadhyay
- , Annesha Sengupta
- & Himadri B. Pakrasi
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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 AccessDistinguishing individual photobodies using Oligopaints reveals thermo-sensitive and -insensitive phytochrome B condensation at distinct subnuclear locations
Photobodies form via the condensation of the light and temperature sensor phytochrome B. Here, the authors label photobodies using nuclear landmarks to demonstrate the nonrandom thermos-sensitive and -insensitive seeding of distinct photobodies.
- Juan Du
- , Keunhwa Kim
- & Meng Chen
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Article
| Open AccessStress-shape misalignment in confluent cell layers
When studying nematic ordering of cells in a monolayer, it is commonly assumed that the principal stress and cell shape axes are tightly coupled. Here, the authors measure cell shape and cell-generated contractile stresses and show that cells in monolayers form correlated, dynamic domains in which the stresses are systematically misaligned with the cell bodies.
- Mehrana R. Nejad
- , Liam J. Ruske
- & Julia M. Yeomans
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Article
| Open AccessLoss of NEDD8 in cancer cells causes vulnerability to immune checkpoint blockade in triple-negative breast cancer
NEDD8 is a ubiquitin-like protein that governs protein neddylation, previously demonstrated to be essential for cell survival. Here the authors show that NEDD8 loss in breast cancer cells is associated with enhanced immunogenicity and increased sensitivity to PD-1 blockade in preclinical cancer models.
- Irineos Papakyriacou
- , Ginte Kutkaite
- & Yumeng Mao
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Article
| Open AccessRinRK1 enhances NF receptors accumulation in nanodomain-like structures at root-hair tip
RinRK1 interacts with NFR1 and NFR5 through their extracellular domains, facilitating a complex with Flot1. This interaction promotes their localization at root hair tip nanodomains, crucial for mediating the rhizobial infection.
- Ning Zhou
- , Xiaolin Li
- & Fang Xie
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Article
| Open AccessDietary L-Glu sensing by enteroendocrine cells adjusts food intake via modulating gut PYY/NPF secretion
Enteroendocrine cells in the gut sense food to regulate feeding behavior. Here, the authors show in Drosophila L-glutamate reduces the frequency of calcium oscillations in enteroendocrine cells and decreases the release of NPF, thereby reducing the activation of a pair of anorexic enteric neurons.
- Junjun Gao
- , Song Zhang
- & Zheng Guo
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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 AccessPhotobody formation spatially segregates two opposing phytochrome B signaling actions of PIF5 degradation and stabilization
Photobodies are plant nuclear bodies containing the photoreceptor phytochrome B. Here, the authors reveal that photobody formation segregates opposing phytochrome B-mediated light-signaling actions into two phase-separated subnuclear compartments
- Ruth Jean Ae Kim
- , De Fan
- & Meng Chen
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Article
| Open AccessPersistent TFIIH binding to non-excised DNA damage causes cell and developmental failure
Hereditary nucleotide excision repair deficiencies cause different cancerous and progeroid disorders of which the exact etiology is not understood. This study finds that prolonged binding of DNA repair factor TFIIH to DNA damage contributes to a more severe phenotype caused by DNA repair deficiency.
- Alba Muniesa-Vargas
- , Carlota Davó-Martínez
- & Hannes Lans
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Article
| Open AccessIFT cargo and motors associate sequentially with IFT trains to enter cilia of C. elegans
Intraflagellar transport is essential for the formation and function of cilia. Here, the authors use single-molecule imaging in live C. elegans to show that transport trains are formed by the sequential attachment of proteins before departing into the cilium.
- Aniruddha Mitra
- , Elizaveta Loseva
- & Erwin J. G. Peterman
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Article
| Open AccessTANGO1 inhibitors reduce collagen secretion and limit tissue scarring
Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring. Here the authors describe membrane permeable peptides that target the interface of TANGO1 and cTAGE5, inhibit secretion of ECM components and could be of therapeutic benefit during wound healing and fibrotic processes.
- Ishier Raote
- , Ann-Helen Rosendahl
- & Vivek Malhotra
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Article
| Open AccessTemporal coordination of the transcription factor response to H2O2 stress
H2O2 stress is known to activate a slew of transcription factors that restore redox balance. Here, the authors use live-cell imaging and single-cell analysis to reveal that the transcription factors that are activated and their timing of activation is dose dependent.
- Elizabeth Jose
- , Woody March-Steinman
- & Andrew L. Paek
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Article
| Open AccessPhosphorylation of the F-BAR protein Hof1 drives septin ring splitting in budding yeast
Cytokinesis in budding yeast is accompanied by a major rearrangement of septins into a double ring. Here, authors show that the F-BAR protein Hof1 contributes to septin remodeling upon its phosphorylation and relocalisation from septins to the division site.
- Maritzaida Varela Salgado
- , Ingrid E. Adriaans
- & Simonetta Piatti
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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 AccessTracing genetic diversity captures the molecular basis of misfolding disease
Pei et al. applied Gaussian process-based machine learning to capture dynamic spatial covariance relationships managed by proteostasis to mediate cooperative folding on a residue basis as a standard model for precision disease management.
- Pei Zhao
- , Chao Wang
- & William E. Balch
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Article
| Open AccessModulation of peroxisomal import by the PEX13 SH3 domain and a proximal FxxxF binding motif
Import of proteins into peroxisomes depends on PEX5, PEX13 and PEX14. Here the authors obtain crystal structures and NMR data to show the recognition of diaromatic peptide motifs on a noncanonical surface of the PEX13 SH3 domain, revealing a dynamic network which modulates peroxisomal matrix import.
- Stefan Gaussmann
- , Rebecca Peschel
- & Michael Sattler
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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 AccessCross-link assisted spatial proteomics to map sub-organelle proteomes and membrane protein topologies
The spatial mapping of proteins can give important functional insights. Here, Zhu et al. develop a cross-linking mass spectrometry-based spatial proteomics method that does not require protein engineering, affords sub-organelle resolution, and elucidates both protein locations and membrane topologies.
- Ying Zhu
- , Kerem Can Akkaya
- & Fan Liu
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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 AccessHost response during unresolved urinary tract infection alters female mammary tissue homeostasis through collagen deposition and TIMP1
Urinary tract infections (UTIs) can elicit systemic host-responses. Here the authors report that, in a mouse model, unresolved UTI is associated with alterations of the mammary tissue, including collagen deposition and hyperplasia.
- Samantha Henry
- , Steven Macauley Lewis
- & Camila Oresco dos Santos
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Article
| Open AccessNerve growth factor receptor limits inflammation to promote remodeling and repair of osteoarthritic joints
Osteoarthritis is a painful and debilitating condition. Here, the authors show that NGFR, a receptor for NGF, restricts NF-κB activation and its deficiency in skeletal cells impairs the remodeling and repair of osteoarthritic joints.
- Lan Zhao
- , Yumei Lai
- & Jian Huang
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Article
| Open AccessReciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry
Unveiling the regulation of mitotic protein degradation is crucial for cancer therapy. Here, the authors reveal that a reciprocal inhibition of PIN1-APC/CCDH1 controls the cell cycle and mitotic protein degradation, offering a synergistic anti-tumor strategy.
- Shizhong Ke
- , Fabin Dang
- & Kun Ping Lu
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Article
| Open AccessAn experimental framework to assess biomolecular condensates in bacteria
The small cell size of bacteria is a key hurdle in studying condensates. To address this challenge, the authors develop an experimental framework to assess bacterial condensates based on how they form, dissolve, tune shape and size, and transition between material states.
- Y Hoang
- , Christopher A. Azaldegui
- & Anthony G. Vecchiarelli
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Article
| Open AccessOptogenetic control of mRNA condensation reveals an intimate link between condensate material properties and functions
Biomolecular condensates play important roles in diverse cellular activities. Here the authors employ optogenetic tool and single-molecule mRNA imaging, showing that sequestering target mRNAs into condensates lead to translation inhibition.
- Min Lee
- , Hyungseok C. Moon
- & Yongdae Shin
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Article
| Open AccessDynamics of DNA damage-induced nuclear inclusions are regulated by SUMOylation of Btn2
Maintaining a healthy nuclear proteome during DNA damage is important but its regulation is poorly understood. The authors here show that a SUMO modification of the small heat shock protein Btn2 regulates yeast nuclear protein sequestration during stress.
- Arun Kumar
- , Veena Mathew
- & Peter C. Stirling
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Article
| Open AccessLipopolysaccharide binding protein resists hepatic oxidative stress by regulating lipid droplet homeostasis
Oxidative stress triggers lipid accumulation in cells by sequestering triglycerides in lipid droplets. Here, the authors show that lipopolysaccharide-binding protein interacts with redox sensor PRDX4 to control lipid-redox balance and promotes triglyceride accumulation in droplets by capturing unsaturated lipids.
- Qilun Zhang
- , Xuting Shen
- & Haoshu Fang
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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 AccessPRPF8-mediated dysregulation of hBrr2 helicase disrupts human spliceosome kinetics and 5´-splice-site selection causing tissue-specific defects
PRPF8 is a hotspot for mutations causing retinitis pigmentosa-type 13. Here the authors generated PRPF8 patient-specific retinal cells, demonstrating an important role for this splicing factor in spliceosome kinetics and 5’ splice site selection.
- Robert Atkinson
- , Maria Georgiou
- & Majlinda Lako
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Article
| Open AccessRegulation by the RNA-binding protein Unkempt at its effector interface
How RNA-binding proteins (RBPs) regulate gene expression via effectors of RNA processing is unclear. Here, the authors dissect the effector interface of an essential RBP, Unkempt, and investigate its contribution to translational control in cells.
- Kriti Shah
- , Shiyang He
- & Jernej Murn
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Article
| Open AccessNardilysin-regulated scission mechanism activates polo-like kinase 3 to suppress the development of pancreatic cancer
Polo-like kinase 3 (Plk3) has a tumor suppressive role through the induction of apoptosis, however, the mechanism underlying its activation is unclear. Here, in pancreatic cancer, the authors show that activation of Plk3 is dependent on its cleavage into p41Plk3, by the metalloendopeptidase nardilysin.
- Jie Fu
- , Jianhua Ling
- & Paul J. Chiao
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Article
| Open AccessAn adaptive biomolecular condensation response is conserved across environmentally divergent species
Cells must respond to environmental changes. In three fungal species adapted to different temperatures, cellular responses are conserved yet tuned to each organism’s thermal niche, including the formation of adaptive biomolecular condensates.
- Samantha Keyport Kik
- , Dana Christopher
- & D. Allan Drummond
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Article
| Open AccessKinetic trapping organizes actin filaments within liquid-like protein droplets
Here the authors perform modelling to reveal that the timescale of actin-VASP interactions plays a critical role in actin ring formation and filament length determines droplet deformation in VASP droplets: predictions from the model were tested against VASP GAB mutant.
- Aravind Chandrasekaran
- , Kristin Graham
- & Padmini Rangamani
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Article
| Open AccessSalmonella exploits membrane reservoirs for invasion of host cells
The plasma membrane of eukaryotic cells can fold inwards to create reservoirs that store or release excess membrane. Zhu et al. show that Salmonella-secreted effectors modulate these reservoirs to facilitate host cell invasion.
- Hongxian Zhu
- , Andrew M. Sydor
- & John H. Brumell
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Article
| Open AccessIntegrated proteomics reveals autophagy landscape and an autophagy receptor controlling PKA-RI complex homeostasis in neurons
The health of brain cells is known to depend on functional autophagy, but the details are unclear. Here, the authors perform systematic proteomic profiling of human and mouse neurons, delineating the landscape of autophagy degradation in brain.
- Xiaoting Zhou
- , You-Kyung Lee
- & Zhenyu Yue
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Article
| Open AccessLDL receptor-related protein 5 selectively transports unesterified polyunsaturated fatty acids to intracellular compartments
The mechanisms transporting fatty acids into the cell are not completely understood. Here, the authors discover a selective transporter for a specific class of lipids, and show its role in regulating neutrophil function during myocardial ischemia-reperfusion injury.
- Wenwen Tang
- , Yi Luan
- & Dianqing Wu
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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 Accessp53 promotes revival stem cells in the regenerating intestine after severe radiation injury
The tumor suppressor p53 is the guardian of the genome. Here, the authors use comprehensive approaches to demonstrate that transient p53 activity induces revival stem cells to promote the regeneration of severely irradiated intestinal epithelium in mice.
- Clara Morral
- , Arshad Ayyaz
- & David G. Kirsch
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Article
| Open AccessEngineering an artificial catch bond using mechanical anisotropy
Catch bonds are unique protein-protein interactions where the bond lifetime increases under external pulling forces. Here, the authors engineer an artificial catch bond based on a non-catch bonding human gut bacterial adhesion protein complex.
- Zhaowei Liu
- , Haipei Liu
- & Michael A. Nash
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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 AccessHalogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus
Modulating amyloid protein phase separation and fibrilization may help in addressing neurodegenerative diseases. This study demonstrates that halogen-doped graphene quantum dots can modulate these processes in TDP-43 in both nucleus and cytoplasm.
- Hong Zhang
- , Huazhang Guo
- & Bin Dai
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Article
| Open AccessGadd45g insufficiency drives the pathogenesis of myeloproliferative neoplasms
Different gene mutations have been reported as drivers for myeloproliferative neoplasms (MPN). Here, the authors show that Gadd45g insufficiency induces MPN in mouse models and associates with MPN in patients.
- Peiwen Zhang
- , Na You
- & Xiaotong Ma
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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 AccessTranslation velocity determines the efficacy of engineered suppressor tRNAs on pathogenic nonsense mutations
An emerging therapeutic strategy is to suppress nonsense mutations with engineered suppressor tRNAs. Here, the authors show that the mRNA translation velocity is a key parameter determining the efficacy of suppressor tRNAs.
- Nikhil Bharti
- , Leonardo Santos
- & Zoya Ignatova
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Article
| Open AccessSeeding the meiotic DNA break machinery and initiating recombination on chromosome axes
Meiotic cells deliberately break their DNA to allow chromosomes to swap genetic material. Here, authors reveal genetically separable pathways controlling the seeding and growth of chromosome-bound protein condensates responsible for DNA breaks.
- Ihsan Dereli
- , Vladyslav Telychko
- & Attila Tóth
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Article
| Open AccessStatins improve cardiac endothelial function to prevent heart failure with preserved ejection fraction through upregulating circRNA-RBCK1
Endothelial dysfunction has been shown to occur in HFpEF and we know that statins can target endothelial dysfunction by inhibiting miR-133a. Here the authors show that statins improve diastolic dysfunction in HFpEF by increasing the levels of a circRNA which, in turns, binds to miR-133a modulating its downstream targets.
- Bin Li
- , Wen-Wu Bai
- & Shuang-Xi Wang
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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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