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Developmental Cell

Bikram Sharma, Lena Ho, Gretchen Hazel Ford, Heidi I Chen, Andrew B Goldstone, Y Joseph Woo, Thomas Quertermous, Bruno Reversade, Kristy Red-Horse
Organogenesis during embryonic development occurs through the differentiation of progenitor cells. This process is extraordinarily accurate, but the mechanisms ensuring high fidelity are poorly understood. Coronary vessels of the mouse heart derive from at least two progenitor pools, the sinus venosus and endocardium. We find that the ELABELA (ELA)-APJ signaling axis is only required for sinus venosus-derived progenitors. Because they do not depend on ELA-APJ, endocardial progenitors are able to expand and compensate for faulty sinus venosus development in Apj mutants, leading to normal adult heart function...
August 31, 2017: Developmental Cell
Marc Bachofner, Tobias Speicher, Roman L Bogorad, Sukalp Muzumdar, Carina P Derrer, Fabrizio Hürlimann, Friederike Böhm, Paolo Nanni, Tobias Kockmann, Ekaterina Kachaylo, Michael Meyer, Susagna Padrissa-Altés, Rolf Graf, Daniel G Anderson, Victor Koteliansky, Ulrich Auf dem Keller, Sabine Werner
The liver is the only organ in mammals that fully regenerates even after major injury. To identify orchestrators of this regenerative response, we performed quantitative large-scale proteomics analysis of cytoplasmic and nuclear fractions from normal versus regenerating mouse liver. Proteins of the ubiquitin-proteasome pathway were rapidly upregulated after two-third hepatectomy, with the ubiquitin ligase Nedd4-1 being a top hit. In vivo knockdown of Nedd4-1 in hepatocytes through nanoparticle-mediated delivery of small interfering RNA caused severe liver damage and inhibition of cell proliferation after hepatectomy, resulting in liver failure...
August 30, 2017: Developmental Cell
Masaki Arata, Kaoru Sugimura, Tadashi Uemura
In contrast to extracellular chemotactic gradients, how cell-adhesion molecules contribute to directing cell migration remains more elusive. Here we studied the collective migration of Drosophila larval epidermal cells (LECs) along the anterior-posterior axis and propose a migrating cell group-autonomous mechanism in which an atypical cadherin Dachsous (Ds) plays a pivotal role. In each abdominal segment, the amount of Ds in each LEC varied along the axis of migration (Ds imbalance), which polarized Ds localization at cell boundaries...
September 11, 2017: Developmental Cell
Coralie Dessauges, Olivier Pertz
Reporting in Developmental Cell, de la Cova et al. (2017) present a biosensor to measure ERK activity dynamics in C. elegans larvae. They find that fate decision signaling involves frequency-modulated, digital ERK activity pulses. These findings may explain how graded morphogen signals are converted into precise and robust cell fate patterns.
September 11, 2017: Developmental Cell
Mingxuan Sun, Rebecca Heald
Incorporating each set of daughter chromosomes into a single nucleus at the end of mitosis is essential for genome stability. In a recent Cell paper, Samwer et al. (2017) show that by non-covalently crosslinking DNA, BAF promotes chromosome coalescence, preventing nuclear membranes from enwrapping individual chromosomes to form micronuclei.
September 11, 2017: Developmental Cell
Paul Lasko
mRNA localization often contributes to translational control. Reporting in Science, Moor et al. (2017) now show that many mRNAs and ribosomes are asymmetrically distributed along the apical-basal axis of enterocytes. Remarkably, when starved mice are fed, mRNAs encoding ribosomal proteins rapidly move to the ribosome-rich apical side to activate translation.
September 11, 2017: Developmental Cell
Stefan Linder
The Arp2/3 complex nucleates branched actin networks and is thought to be essential for macrophage migration and phagocytosis. In this issue of Developmental Cell, Rotty et al. (2017) show that there is only a surprisingly specific requirement for Arp2/3 in integrin-dependent macrophage functions, including CR3 phagocytosis and haptotaxis on fibronectin.
September 11, 2017: Developmental Cell
Lauren M Goddard, Mark L Kahn
Detailed molecular pathways for the specific growth of arteries and lymphatic vessels have been identified, but the mechanisms controlling venous vessel growth have been obscure. Tischfield and colleagues (2017) shed new light on this problem by identifying a role for BMP signaling in development of the cerebral venous system.
September 11, 2017: Developmental Cell
Aline Bonnet, Guillaume Lambert, Sylvain Ernest, François Xavier Dutrieux, Fanny Coulpier, Sophie Lemoine, Riadh Lobbardi, Frédéric Marc Rosa
Skeletal muscle contraction is mediated by myofibrils, complex multi-molecular scaffolds structured into repeated units, the sarcomeres. Myofibril structure and function have been extensively studied, but the molecular processes regulating its formation within the differentiating muscle cell remain largely unknown. Here we show in zebrafish that genetic interference with the Quaking RNA-binding proteins disrupts the initial steps of myofibril assembly without affecting early muscle differentiation. Using RNA sequencing, we demonstrate that Quaking is required for accumulation of the muscle-specific tropomyosin-3 transcript, tpm3...
September 11, 2017: Developmental Cell
Jeremy D Rotty, Hailey E Brighton, Stephanie L Craig, Sreeja B Asokan, Ning Cheng, Jenny P Ting, James E Bear
The Arp2/3 complex nucleates branched actin, forming networks involved in lamellipodial protrusion, phagocytosis, and cell adhesion. We derived primary bone marrow macrophages lacking Arp2/3 complex (Arpc2(-/-)) and directly tested its role in macrophage functions. Despite protrusion and actin assembly defects, Arpc2(-/-) macrophages competently phagocytose via FcR and chemotax toward CSF and CX3CL1. However, CR3 phagocytosis and fibronectin haptotaxis, both integrin-dependent processes, are disrupted. Integrin-responsive actin assembly and αM/β2 integrin localization are compromised in Arpc2(-/-) cells...
September 11, 2017: Developmental Cell
Xiaohong Wang, Aida Freire Valls, Géza Schermann, Ying Shen, Ivan M Moya, Laura Castro, Severino Urban, Gergely M Solecki, Frank Winkler, Lars Riedemann, Rakesh K Jain, Massimilano Mazzone, Thomas Schmidt, Tamás Fischer, Georg Halder, Carmen Ruiz de Almodóvar
Vascular endothelial growth factor (VEGF) is a major driver of blood vessel formation. However, the signal transduction pathways culminating in the biological consequences of VEGF signaling are only partially understood. Here, we show that the Hippo pathway effectors YAP and TAZ work as crucial signal transducers to mediate VEGF-VEGFR2 signaling during angiogenesis. We demonstrate that YAP/TAZ are essential for vascular development as endothelium-specific deletion of YAP/TAZ leads to impaired vascularization and embryonic lethality...
September 11, 2017: Developmental Cell
Max A Tischfield, Caroline D Robson, Nicole M Gilette, Shek Man Chim, Folasade A Sofela, Michelle M DeLisle, Alon Gelber, Brenda J Barry, Sarah MacKinnon, Linda R Dagi, Jeremy Nathans, Elizabeth C Engle
Dural cerebral veins (CV) are required for cerebrospinal fluid reabsorption and brain homeostasis, but mechanisms that regulate their growth and remodeling are unknown. We report molecular and cellular processes that regulate dural CV development in mammals and describe venous malformations in humans with craniosynostosis and TWIST1 mutations that are recapitulated in mouse models. Surprisingly, Twist1 is dispensable in endothelial cells but required for specification of osteoprogenitor cells that differentiate into preosteoblasts that produce bone morphogenetic proteins (BMPs)...
September 11, 2017: Developmental Cell
Frederic Koch, Manuela Scholze, Lars Wittler, Dennis Schifferl, Smita Sudheer, Phillip Grote, Bernd Timmermann, Karol Macura, Bernhard G Herrmann
The spinal cord and mesodermal tissues of the trunk such as the vertebral column and skeletal musculature derive from neuro-mesodermal progenitors (NMPs). Sox2, Brachyury (T), and Tbx6 have been correlated with NMP potency and lineage choice; however, their exact role and interaction in these processes have not yet been revealed. Here we present a global analysis of NMPs and their descending lineages performed on purified cells from embryonic day 8.5 wild-type and mutant embryos. We show that T, cooperatively with WNT signaling, controls the progenitor state and the switch toward the mesodermal fate...
September 11, 2017: Developmental Cell
Claire de la Cova, Robert Townley, Sergi Regot, Iva Greenwald
Kinase translocation reporters (KTRs) are genetically encoded fluorescent activity sensors that convert kinase activity into a nucleocytoplasmic shuttling equilibrium for visualizing single-cell signaling dynamics. Here, we adapt the first-generation KTR for extracellular signal-regulated kinase (ERK) to allow easy implementation in vivo. This sensor, "ERK-nKTR," allows quantitative and qualitative assessment of ERK activity by analysis of individual nuclei and faithfully reports ERK activity during development and neural function in diverse cell contexts in Caenorhabditis elegans...
September 11, 2017: Developmental Cell
Daniel J Dickinson, Francoise Schwager, Lionel Pintard, Monica Gotta, Bob Goldstein
Regulated protein-protein interactions are critical for cell signaling, differentiation, and development. For the study of dynamic regulation of protein interactions in vivo, there is a need for techniques that can yield time-resolved information and probe multiple protein binding partners simultaneously, using small amounts of starting material. Here we describe a single-cell protein interaction assay. Single-cell lysates are generated at defined time points and analyzed using single-molecule pull-down, yielding information about dynamic protein complex regulation in vivo...
August 21, 2017: Developmental Cell
Ronen Blecher, Sharon Krief, Tal Galili, Inbal E Biton, Tomer Stern, Eran Assaraf, Ditsa Levanon, Elena Appel, Yoram Anekstein, Gabriel Agar, Yoram Groner, Elazar Zelzer
Maintaining posture requires tight regulation of the position and orientation of numerous spinal components. Yet, surprisingly little is known about this regulatory mechanism, whose failure may result in spinal deformity as in adolescent idiopathic scoliosis. Here, we use genetic mouse models to demonstrate the involvement of proprioception in regulating spine alignment. Null mutants for Runx3 transcription factor, which lack TrkC neurons connecting between proprioceptive mechanoreceptors and spinal cord, developed peripubertal scoliosis not preceded by vertebral dysplasia or muscle asymmetry...
August 21, 2017: Developmental Cell
Jesús Romero-Pozuelo, Constantinos Demetriades, Phillip Schroeder, Aurelio A Teleman
The molecular mechanisms regulating animal tissue size during development are unclear. This question has been extensively studied in the Drosophila wing disc. Although cell growth is regulated by the kinase TORC1, no readout exists to visualize TORC1 activity in situ in Drosophila. Both the cell cycle and the morphogen Dpp are linked to tissue growth, but whether they regulate TORC1 activity is not known. We develop here an anti-phospho-dRpS6 antibody that detects TORC1 activity in situ. We find, unexpectedly, that TORC1 activity in the wing disc is patchy...
August 21, 2017: Developmental Cell
Wonho Kim, Yoon-Gu Jang, Jinsung Yang, Jongkyeong Chung
Target of rapamycin complex 1 (TORC1) regulates cell growth in response to nutrients and growth factors. Although TORC1 signaling has been thoroughly studied at the cellular level, the regulation of TORC1 in multicellular tissues and organs has remained elusive. Here we found that TORC1 is selectively activated in the second mitotic wave (SMW), the terminal synchronous cell division, of the developing Drosophila eye. We demonstrated that Hedgehog (Hh) signaling regulates TORC1 through E2F1 and the cyclin D/Cdk4 complex in the SMW, and this regulation is independent from insulin and amino acid signaling pathways...
August 21, 2017: Developmental Cell
Juli Liu, Yang Li, Bo Lin, Yi Sheng, Lei Yang
Cardiogenesis processes in human and animals have differential dynamics, suggesting the existence of species-specific regulators during heart development. However, it remains a challenge to discover the human-specific cardiac regulatory genes, given that most coding genes are conserved. Here, we report the identification of a human-specific long noncoding RNA, Heart Brake LncRNA 1 (HBL1), which regulates cardiomyocyte development from human induced pluripotent stem cells (hiPSCs). Overexpression of HBL1 repressed, whereas knockdown and knockout of HBL1 increased, cardiomyocyte differentiation from hiPSCs...
August 21, 2017: Developmental Cell
David Jukam, S Ali M Shariati, Jan M Skotheim
The first major developmental transition in vertebrate embryos is the maternal-to-zygotic transition (MZT) when maternal mRNAs are degraded and zygotic transcription begins. During the MZT, the embryo takes charge of gene expression to control cell differentiation and further development. This spectacular organismal transition requires nuclear reprogramming and the initiation of RNAPII at thousands of promoters. Zygotic genome activation (ZGA) is mechanistically coordinated with other embryonic events, including changes in the cell cycle, chromatin state, and nuclear-to-cytoplasmic component ratios...
August 21, 2017: Developmental Cell
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