"All Cells Come from Cells" ∗.
"All Cells Come from Cells"∗. Dev Cell. 2019 Dec 02;51(5):543 Authors: Sollier J PMID: 31794713 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - December 2, 2019 Category: Cytology Authors: Sollier J Tags: Dev Cell Source Type: research

LDAF1 Holds the Key to Seipin Function.
Abstract Seipin is an ER protein important for the assembly of cytoplasmic lipid droplets. In this issue of Developmental Cell, Chung et al. (2019) show that a stable seipin-binding protein, LDAF1/promethin, functions with seipin by attracting triacylglycerol and then allowing this lipid to accumulate and partition into nascent droplets. PMID: 31794714 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - December 2, 2019 Category: Cytology Authors: Goodman JM Tags: Dev Cell Source Type: research

Balancing Act: Cell Polarity and Shape Compete to Ensure Robust Development.
Abstract In this issue of Developmental Cell, Niwayama et al. (2019) describe a model in which cell polarity and cell shape compete to determine the orientation of cell division in the pre-implantation mouse embryo. This model explains how simple cell-intrinsic rules lead to robust tissue-level morphogenesis and lineage segregation. PMID: 31794715 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - December 2, 2019 Category: Cytology Authors: Murrow LM, Gartner ZJ Tags: Dev Cell Source Type: research

Prominin-2 Suppresses Ferroptosis Sensitivity.
Abstract Ferroptosis causes clinically relevant amounts of necrosis during the course of heart attacks and acute kidney injury. However, ferroptosis is still a very young research field. In this issue of Developmental Cell, Brown et al. describe the pentaspan membrane glycoprotein prominin-2 as a novel endogenous ferroptosis inhibitor. PMID: 31794716 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - December 2, 2019 Category: Cytology Authors: Belavgeni A, Bornstein SR, Linkermann A Tags: Dev Cell Source Type: research

Age-Onset Phosphorylation of a Minor Actin Variant Promotes Intestinal Barrier Dysfunction.
Abstract Age-associated decay of intercellular interactions impairs the cells' capacity to tightly associate within tissues and form a functional barrier. This barrier dysfunction compromises organ physiology and contributes to systemic failure. The actin cytoskeleton represents a key determinant in maintaining tissue architecture. Yet, it is unclear how age disrupts the actin cytoskeleton and how this, in turn, promotes mortality. Here, we show that an uncharacterized phosphorylation of a low-abundant actin variant, ACT-5, compromises integrity of the C. elegans intestinal barrier and accelerates pathog...
Source: Developmental Cell - December 2, 2019 Category: Cytology Authors: Egge N, Arneaud SLB, Wales P, Mihelakis M, McClendon J, Fonseca RS, Savelle C, Gonzalez I, Ghorashi A, Yadavalli S, Lehman WJ, Mirzaei H, Douglas PM Tags: Dev Cell Source Type: research

ERK1/2 Phosphorylation of FHOD Connects Signaling and Nuclear Positioning Alternations in Cardiac Laminopathy.
Abstract Mutations in the lamin A/C gene (LMNA) cause cardiomyopathy and also disrupt nuclear positioning in fibroblasts. LMNA mutations causing cardiomyopathy elevate ERK1/2 activity in the heart, and inhibition of the ERK1/2 kinase activity ameliorates pathology, but the downstream effectors remain largely unknown. We now show that cardiomyocytes from mice with an Lmna mutation and elevated cardiac ERK1/2 activity have altered nuclear positioning. In fibroblasts, ERK1/2 activation negatively regulated nuclear movement by phosphorylating S498 of FHOD1. Expression of an unphosphorylatable FHOD1 variant rescued the...
Source: Developmental Cell - December 2, 2019 Category: Cytology Authors: Antoku S, Wu W, Joseph LC, Morrow JP, Worman HJ, Gundersen GG Tags: Dev Cell Source Type: research

A Role for Retrotransposon LINE-1 in Fetal Oocyte Attrition in Mice.
PMID: 31794719 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - December 2, 2019 Category: Cytology Authors: Malki S, van der Heijden GW, O'Donnell KA, Martin SL, Bortvin A Tags: Dev Cell Source Type: research

TGF- β Signaling Promotes Tissue Formation during Cardiac Valve Regeneration in Adult Zebrafish.
TGF-β Signaling Promotes Tissue Formation during Cardiac Valve Regeneration in Adult Zebrafish. Dev Cell. 2019 Nov 26;: Authors: Bensimon-Brito A, Ramkumar S, Boezio GLM, Guenther S, Kuenne C, Helker CSM, Sánchez-Iranzo H, Iloska D, Piesker J, Pullamsetti S, Mercader N, Beis D, Stainier DYR Abstract Cardiac valve disease can lead to severe cardiac dysfunction and is thus a frequent cause of morbidity and mortality. Its main treatment is valve replacement, which is currently greatly limited by the poor recellularization and tissue formation potential of the implanted valves. As we still lac...
Source: Developmental Cell - November 26, 2019 Category: Cytology Authors: Bensimon-Brito A, Ramkumar S, Boezio GLM, Guenther S, Kuenne C, Helker CSM, Sánchez-Iranzo H, Iloska D, Piesker J, Pullamsetti S, Mercader N, Beis D, Stainier DYR Tags: Dev Cell Source Type: research

Dkk1 Controls Cell-Cell Interaction through Regulation of Non-nuclear β-Catenin Pools.
Dkk1 Controls Cell-Cell Interaction through Regulation of Non-nuclear β-Catenin Pools. Dev Cell. 2019 Nov 26;: Authors: Johansson M, Giger FA, Fielding T, Houart C Abstract Dickkopf-1 (Dkk1) is a secreted Wnt antagonist with a well-established role in head induction during development. Numerous studies have emerged implicating Dkk1 in various malignancies and neurodegenerative diseases through an unknown mechanism. Using zebrafish gastrulation as a model for collective cell migration, we unveil such a mechanism, identifying a role for Dkk1 in control of cell connectivity and polarity in vivo...
Source: Developmental Cell - November 26, 2019 Category: Cytology Authors: Johansson M, Giger FA, Fielding T, Houart C Tags: Dev Cell Source Type: research

N-WASP Guides Cancer Cells toward LPA.
Abstract The actin remodeling factor N-WASP is best known as an Arp2/3 complex activator in processes like endocytosis, extracellular matrix degradation, and host-pathogen interaction. In this issue of Developmental Cell, Juin et al. establish a novel trafficking function for N-WASP in driving lysophosphatidic acid-dependent chemotaxis and metastasis of pancreatic cancer cells. PMID: 31743660 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - November 18, 2019 Category: Cytology Authors: Rottner K, Schaks M Tags: Dev Cell Source Type: research

Role Reversal: A Pro-metastatic Function of E-Cadherin.
Abstract Carcinoma cells often acquire mobility and invasiveness by undergoing epithelial-to-mesenchymal transition, and yet most metastatic lesions remain epithelial in nature. Recently, in Nature, Padmanaban et al. (2019) demonstrated that the quintessential epithelial marker E-cadherin promotes metastasis of invasive ductal breast carcinoma by enhancing the survival of tumor cells. PMID: 31743661 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - November 18, 2019 Category: Cytology Authors: Shen M, Kang Y Tags: Dev Cell Source Type: research

Tricalbin-Mediated Contact Sites Control ER Curvature to Maintain Plasma Membrane Integrity.
ndez-Busnadiego R Abstract Membrane contact sites (MCS) between the endoplasmic reticulum (ER) and the plasma membrane (PM) play fundamental roles in all eukaryotic cells. ER-PM MCS are particularly abundant in Saccharomyces cerevisiae, where approximately half of the PM surface is covered by cortical ER (cER). Several proteins, including Ist2, Scs2/22, and Tcb1/2/3 are implicated in cER formation, but the specific roles of these molecules are poorly understood. Here, we use cryo-electron tomography to show that ER-PM tethers are key determinants of cER morphology. Notably, Tcb proteins (tricalbins) form peaks of ...
Source: Developmental Cell - November 18, 2019 Category: Cytology Authors: Collado J, Kalemanov M, Campelo F, Bourgoint C, Thomas F, Loewith R, Martínez-Sánchez A, Baumeister W, Stefan CJ, Fernández-Busnadiego R Tags: Dev Cell Source Type: research

Tricalbins Contribute to Cellular Lipid Flux and Form Curved ER-PM Contacts that Are Bridged by Rod-Shaped Structures.
Abstract Lipid flow between cellular organelles occurs via membrane contact sites. Extended-synaptotagmins, known as tricalbins in yeast, mediate lipid transfer between the endoplasmic reticulum (ER) and plasma membrane (PM). How these proteins regulate membrane architecture to transport lipids across the aqueous space between bilayers remains unknown. Using correlative microscopy, electron cryo-tomography, and high-throughput genetics, we address the interplay of architecture and function in budding yeast. We find that ER-PM contacts differ in protein composition and membrane morphology, not in intermembrane dist...
Source: Developmental Cell - November 18, 2019 Category: Cytology Authors: Hoffmann PC, Bharat TAM, Wozny MR, Boulanger J, Miller EA, Kukulski W Tags: Dev Cell Source Type: research

Coronary Revascularization During Heart Regeneration Is Regulated by Epicardial and Endocardial Cues and Forms a Scaffold for Cardiomyocyte Repopulation.
r DYR Abstract Defective coronary network function and insufficient blood supply are both cause and consequence of myocardial infarction. Efficient revascularization after infarction is essential to support tissue repair and function. Zebrafish hearts exhibit a remarkable ability to regenerate, and coronary revascularization initiates within hours of injury, but how this process is regulated remains unknown. Here, we show that revascularization requires a coordinated multi-tissue response culminating with the formation of a complex vascular network available as a scaffold for cardiomyocyte repopulation. During a p...
Source: Developmental Cell - November 18, 2019 Category: Cytology Authors: Marín-Juez R, El-Sammak H, Helker CSM, Kamezaki A, Mullapuli ST, Bibli SI, Foglia MJ, Fleming I, Poss KD, Stainier DYR Tags: Dev Cell Source Type: research

Emergence of a Bilaterally Symmetric Pattern from Chiral Components in the Planarian Epidermis.
Abstract Most animals exhibit mirror-symmetric body plans, yet the molecular constituents from which they are formed are often chiral. In planarian flatworms, centrioles are arranged in a bilaterally symmetric pattern across the ventral epidermis. Here, we found that this pattern is generated by a network of centrioles with prominent chiral asymmetric properties. We identify centriole components required for establishing asymmetric connections between centrioles and balancing their effects to align centrioles along polarity fields. SMED-ODF2, SMED-VFL1, and SMED-VFL3 affect the assembly of centriole appendages tha...
Source: Developmental Cell - November 18, 2019 Category: Cytology Authors: Basquin C, Ershov D, Gaudin N, Vu HT, Louis B, Papon JF, Orfila AM, Mansour S, Rink JC, Azimzadeh J Tags: Dev Cell Source Type: research

Dynamic Polarization of the Multiciliated Planarian Epidermis between Body Plan Landmarks.
JC Abstract Polarity is a universal design principle of biological systems that manifests at all organizational scales, yet its coordination across scales remains poorly understood. Here, we make use of the extreme anatomical plasticity of planarian flatworms to probe the interplay between global body plan polarity and local cell polarity. Our quantitative analysis of ciliary rootlet orientation in the epidermis reveals a dynamic polarity field with head and tail as independent determinants of anteroposterior (A/P) polarization and the body margin as determinant of mediolateral (M/L) polarization. Mathematical mo...
Source: Developmental Cell - November 18, 2019 Category: Cytology Authors: Vu HT, Mansour S, Kücken M, Blasse C, Basquin C, Azimzadeh J, Myers EW, Brusch L, Rink JC Tags: Dev Cell Source Type: research

Mutations in ANKLE2, a ZIKA Virus Target, Disrupt an Asymmetric Cell Division Pathway in Drosophila Neuroblasts to Cause Microcephaly.
Abstract The apical Par complex, which contains atypical protein kinase C (aPKC), Bazooka (Par-3), and Par-6, is required for establishing polarity during asymmetric division of neuroblasts in Drosophila, and its activity depends on L(2)gl. We show that loss of Ankle2, a protein associated with microcephaly in humans and known to interact with Zika protein NS4A, reduces brain volume in flies and impacts the function of the Par complex. Reducing Ankle2 levels disrupts endoplasmic reticulum (ER) and nuclear envelope morphology, releasing the kinase Ballchen-VRK1 into the cytosol. These defects are associated with re...
Source: Developmental Cell - November 14, 2019 Category: Cytology Authors: Link N, Chung H, Jolly A, Withers M, Tepe B, Arenkiel BR, Shah PS, Krogan NJ, Aydin H, Geckinli BB, Tos T, Isikay S, Tuysuz B, Mochida GH, Thomas AX, Clark RD, Mirzaa GM, Lupski JR, Bellen HJ Tags: Dev Cell Source Type: research

Adult Drosophila Lack Hematopoiesis but Rely on a Blood Cell Reservoir at the Respiratory Epithelia to Relay Infection Signals to Surrounding Tissues.
r K Abstract The use of adult Drosophila melanogaster as a model for hematopoiesis or organismal immunity has been debated. Addressing this question, we identify an extensive reservoir of blood cells (hemocytes) at the respiratory epithelia (tracheal air sacs) of the thorax and head. Lineage tracing and functional analyses demonstrate that the majority of adult hemocytes are phagocytic macrophages (plasmatocytes) from the embryonic lineage that parallels vertebrate tissue macrophages. Surprisingly, we find no sign of adult hemocyte expansion. Instead, hemocytes play a role in relaying an innate immune respons...
Source: Developmental Cell - November 14, 2019 Category: Cytology Authors: Sanchez Bosch P, Makhijani K, Herboso L, Gold KS, Baginsky R, Woodcock KJ, Alexander B, Kukar K, Corcoran S, Jacobs T, Ouyang D, Wong C, Ramond EJV, Rhiner C, Moreno E, Lemaitre B, Geissmann F, Brückner K Tags: Dev Cell Source Type: research

Prominin2 Drives Ferroptosis Resistance by Stimulating Iron Export.
Abstract Ferroptosis, regulated cell death characterized by the iron-dependent accumulation of lethal lipid reactive oxygen species, contributes to tissue homeostasis and numerous pathologies, and it may be exploited for therapy. Cells differ in their sensitivity to ferroptosis, however, and a key challenge is to understand mechanisms that contribute to resistance. Using RNA-seq to identify genes that contribute to ferroptosis resistance, we discovered that pro-ferroptotic stimuli, including inhibition of the lipid hydroperoxidase GPX4 and detachment from the extracellular matrix, induce expression of prominin2, a...
Source: Developmental Cell - November 13, 2019 Category: Cytology Authors: Brown CW, Amante JJ, Chhoy P, Elaimy AL, Liu H, Zhu LJ, Baer CE, Dixon SJ, Mercurio AM Tags: Dev Cell Source Type: research

A Tug-of-War between Cell Shape and Polarity Controls Division Orientation to Ensure Robust Patterning in the Mouse Blastocyst.
agi T Abstract Oriented cell division patterns tissues by modulating cell position and fate. While cell geometry, junctions, cortical tension, and polarity are known to control division orientation, relatively little is known about how these are coordinated to ensure robust patterning. Here, we systematically characterize cell division, volume, and shape changes during mouse pre-implantation development by in toto live imaging. The analysis leads us to a model in which the apical domain competes with cell shape to determine division orientation. Two key predictions of the model are verified experimentally: when ou...
Source: Developmental Cell - November 13, 2019 Category: Cytology Authors: Niwayama R, Moghe P, Liu YJ, Fabrèges D, Buchholz F, Piel M, Hiiragi T Tags: Dev Cell Source Type: research

Lumen Expansion Facilitates Epiblast-Primitive Endoderm Fate Specification during Mouse Blastocyst Formation.
Abstract Epithelial tissues typically form lumina. In mammalian blastocysts, in which the first embryonic lumen forms, many studies have investigated how the cell lineages are specified through genetics and signaling, whereas potential roles of the fluid lumen have yet to be investigated. We discover that in mouse pre-implantation embryos at the onset of lumen formation, cytoplasmic vesicles are secreted into intercellular space. The segregation of epiblast and primitive endoderm directly follows lumen coalescence. Notably, pharmacological and biophysical perturbation of lumen expansion impairs the specification a...
Source: Developmental Cell - November 12, 2019 Category: Cytology Authors: Ryan AQ, Chan CJ, Graner F, Hiiragi T Tags: Dev Cell Source Type: research

An ECM-to-Nucleus Signaling Pathway Activates Lysosomes for C.  elegans Larval Development.
An ECM-to-Nucleus Signaling Pathway Activates Lysosomes for C. elegans Larval Development. Dev Cell. 2019 Nov 12;: Authors: Miao R, Li M, Zhang Q, Yang C, Wang X Abstract Lysosomes degrade macromolecular cargos, recycle catabolites, and serve as signaling platforms to maintain cell homeostasis, but their role at the tissue level is unclear. Here, we investigate lysosome regulation and function during C. elegans molting, a specialized extracellular matrix (ECM) remodeling process essential for larval development. We found that lysosomes are specifically activated in the epidermis at molt when...
Source: Developmental Cell - November 12, 2019 Category: Cytology Authors: Miao R, Li M, Zhang Q, Yang C, Wang X Tags: Dev Cell Source Type: research

Parallel Processing of Two Mechanosensory Modalities by a Single Neuron in C.  elegans.
Parallel Processing of Two Mechanosensory Modalities by a Single Neuron in C. elegans. Dev Cell. 2019 Nov 08;: Authors: Tao L, Porto D, Li Z, Fechner S, Lee SA, Goodman MB, Xu XZS, Lu H, Shen K Abstract Neurons convert synaptic or sensory inputs into cellular outputs. It is not well understood how a single neuron senses, processes multiple stimuli, and generates distinct neuronal outcomes. Here, we describe the mechanism by which the C. elegans PVD neurons sense two mechanical stimuli: external touch and proprioceptive body movement. These two stimuli are detected by distinct mechanosensitiv...
Source: Developmental Cell - November 8, 2019 Category: Cytology Authors: Tao L, Porto D, Li Z, Fechner S, Lee SA, Goodman MB, Xu XZS, Lu H, Shen K Tags: Dev Cell Source Type: research

Katanin Grips the β-Tubulin Tail through an Electropositive Double Spiral to Sever Microtubules.
Katanin Grips the β-Tubulin Tail through an Electropositive Double Spiral to Sever Microtubules. Dev Cell. 2019 Nov 08;: Authors: Zehr EA, Szyk A, Szczesna E, Roll-Mecak A Abstract The AAA ATPase katanin severs microtubules. It is critical in cell division, centriole biogenesis, and neuronal morphogenesis. Its mutation causes microcephaly. The microtubule templates katanin hexamerization and activates its ATPase. The structural basis for these activities and how they lead to severing is unknown. Here, we show that β-tubulin tails are necessary and sufficient for severing. Cryoelectron micros...
Source: Developmental Cell - November 8, 2019 Category: Cytology Authors: Zehr EA, Szyk A, Szczesna E, Roll-Mecak A Tags: Dev Cell Source Type: research

Highly Efficient CRISPR-Cas9-Based Methods for Generating Deletion Mutations and F0 Embryos that Lack Gene Function in Zebrafish.
Abstract Inconsistent activity limits the use of CRISPR-Cas9 in zebrafish. We show supernumerary guanine nucleotides at the 5' ends of single guide RNAs (sgRNAs) account for diminished CRISPR-Cas9 activity in zebrafish embryos. Genomic sequences can be targeted consistently with extremely high efficiency using Cas9 ribonucleoproteins (RNPs) containing either a sgRNA molecule or a synthetic crRNA:tracrRNA duplex that perfectly matches the protospacer target site. Following injection of zebrafish eggs with such RNPs, virtually every copy of a targeted locus harbors an induced indel mutation. Loss of gene function is...
Source: Developmental Cell - November 7, 2019 Category: Cytology Authors: Hoshijima K, Jurynec MJ, Klatt Shaw D, Jacobi AM, Behlke MA, Grunwald DJ Tags: Dev Cell Source Type: research

LDAF1 and Seipin Form a Lipid Droplet Assembly Complex.
Abstract Lipid droplets (LDs) originate from the endoplasmic reticulum (ER) to store triacylglycerol (TG) and cholesterol esters. The ER protein seipin was shown to localize to ER-LD contacts soon after LDs form, but what determines the sites of initial LD biogenesis in the ER is unknown. Here, we identify TMEM159, now re-named lipid droplet assembly factor 1 (LDAF1), as an interaction partner of seipin. Together, LDAF1 and seipin form an ∼600 kDa oligomeric complex that copurifies with TG. LDs form at LDAF1-seipin complexes, and re-localization of LDAF1 to the plasma membrane co-recruits seipin and ...
Source: Developmental Cell - November 6, 2019 Category: Cytology Authors: Chung J, Wu X, Lambert TJ, Lai ZW, Walther TC, Farese RV Tags: Dev Cell Source Type: research

Diving Deep into the Adult Mouse Kidney.
Abstract In this issue of Developmental Cell, Ransick et al. (2019) provide a comprehensive anatomically guided single-cell dataset from adult mouse kidney, representing the most detailed analysis of the cellular heterogeneity and lineage relationship of cells in the adult mouse kidney published to date. PMID: 31689383 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - November 4, 2019 Category: Cytology Authors: Little MH Tags: Dev Cell Source Type: research

Homolog Pairing at the Push of a Button.
Abstract Homologous chromosomes pair in somatic cells in Drosophila, but how this occurs is poorly understood. In this issue of Developmental Cell, Viets et al. (2019) show that proteins and chromatin structure mediate pairing and argue against a DNA sequence-based mechanism. PMID: 31689384 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - November 4, 2019 Category: Cytology Authors: Bateman JR, Kassis JA Tags: Dev Cell Source Type: research

Lifting Each Other Up: Epidermal Stem Cells in Tissue Homeostasis.
Abstract Multiple stem cells maintain and repair tissues, yet how they communicate is not well understood. In this issue of Developmental Cell, Veniaminova et al. (2019) report that each sebaceous gland is maintained by local stem cells and that Notch signaling regulates multiple aspects of their function, revealing tissue homeostasis mechanisms. PMID: 31689385 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - November 4, 2019 Category: Cytology Authors: Horsley V Tags: Dev Cell Source Type: research

Single-Cell Profiling Reveals Sex, Lineage, and Regional Diversity in the Mouse Kidney.
AP Abstract Chronic kidney disease affects 10% of the population with notable differences in ethnic and sex-related susceptibility to kidney injury and disease. Kidney dysfunction leads to significant morbidity and mortality and chronic disease in other organ systems. A mouse-organ-centered understanding underlies rapid progress in human disease modeling and cellular approaches to repair damaged systems. To enhance an understanding of the mammalian kidney, we combined anatomy-guided single-cell RNA sequencing of the adult male and female mouse kidney with in situ expression studies and cell lineage tracing. These...
Source: Developmental Cell - November 4, 2019 Category: Cytology Authors: Ransick A, Lindström NO, Liu J, Zhu Q, Guo JJ, Alvarado GF, Kim AD, Black HG, Kim J, McMahon AP Tags: Dev Cell Source Type: research

An Ancient CFTR Ortholog Informs Molecular Evolution in ABC Transporters.
Abstract The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel central to the development of secretory diarrhea and cystic fibrosis. The oldest CFTR ortholog identified is from dogfish shark, which retains similar structural and functional characteristics to the mammalian protein, thereby highlighting CFTR's critical role in regulating epithelial ion transport in vertebrates. However, the identification of an early CFTR ortholog with altered structure or function would provide critical insight into the evolution of epithelial anion transport. Here, we describe the earliest known CFTR...
Source: Developmental Cell - October 29, 2019 Category: Cytology Authors: Cui G, Hong J, Chung-Davidson YW, Infield D, Xu X, Li J, Simhaev L, Khazanov N, Stauffer B, Imhoff B, Cottrill K, Blalock JE, Li W, Senderowitz H, Sorscher E, McCarty NA, Gaggar A Tags: Dev Cell Source Type: research

N-WASP Control of LPAR1 Trafficking Establishes Response to Self-Generated LPA Gradients to Promote Pancreatic Cancer Cell Metastasis.
We describe a signaling loop whereby N-WASP and the endocytic adapter SNX18 promote lysophosphatidic acid-induced RhoA-mediated contractility and force generation by controlling lysophosphatidic acid receptor recycling and preventing degradation. This chemotactic loop drives collagen remodeling, tumor invasion, and metastasis and could be an important target against pancreatic cancer spread. PMID: 31668663 [PubMed - as supplied by publisher] (Source: Developmental Cell)
Source: Developmental Cell - October 24, 2019 Category: Cytology Authors: Juin A, Spence HJ, Martin KJ, McGhee E, Neilson M, Cutiongco MFA, Gadegaard N, Mackay G, Fort L, Lilla S, Kalna G, Thomason P, Koh YWH, Norman JC, Insall RH, Machesky LM Tags: Dev Cell Source Type: research

TADs for Life: Chromatin Domain Organization Regulates Lifespan in C.  elegans.
This study sheds light on the mechanisms of domain formation in C. elegans and how these features affect physiology. PMID: 31639364 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - October 21, 2019 Category: Cytology Authors: Dixon JR Tags: Dev Cell Source Type: research

Conducting Chromatin Motion: Actin Dynamizes Contents of the Oocyte Nucleus.
Abstract Architecture of the nucleus is intimately linked to fundamental cellular processes carried out within it, such as maintenance of genome stability and gene expression. In this issue of Developmental Cell, Almonacid et al. (2019) show that actin-dependent shape fluctuations of the oocyte nucleus promote the movement of chromatin inside the nucleoplasm. PMID: 31639365 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - October 21, 2019 Category: Cytology Authors: Mogessie B Tags: Dev Cell Source Type: research

Probing the Functional Role of Physical Motion in Development.
Abstract Spatiotemporal organization during development has frequently been proposed to be explainable by reaction-transport models, where biochemical reactions couple to physical motion. However, whereas genetic tools allow causality of molecular players to be dissected via perturbation experiments, the functional role of physical transport processes, such as diffusion and cytoplasmic streaming, frequently remains untestable. This Perspective explores the challenges of validating reaction-transport hypotheses and highlights new opportunities provided by perturbation approaches that specifically target physical tr...
Source: Developmental Cell - October 21, 2019 Category: Cytology Authors: Kreysing M Tags: Dev Cell Source Type: research

Differential Expression of a Classic Cadherin Directs Tissue-Level Contractile Asymmetry during Neural Tube Closure.
Abstract Embryos control force generation at tissue boundaries, but how they do so remains poorly understood. Here we show how tissue-specific expression of the type II cadherin, Cadherin2, patterns actomyosin contractility along tissue boundaries to control zippering and neural tube closure in the basal chordate, Ciona robusta. Cadherin2 is differentially expressed and homotypically enriched in neural cells along the neural/epidermal (Ne/Epi) boundary, where RhoA and myosin are activated during zipper progression. Homotypically enriched Cadherin2 sequesters the Rho GTPase-activating protein, Gap21/23, to homotypi...
Source: Developmental Cell - October 21, 2019 Category: Cytology Authors: Hashimoto H, Munro E Tags: Dev Cell Source Type: research

Reconstruction of the Global Neural Crest Gene Regulatory Network In  Vivo.
Reconstruction of the Global Neural Crest Gene Regulatory Network In Vivo. Dev Cell. 2019 Oct 21;51(2):255-276.e7 Authors: Williams RM, Candido-Ferreira I, Repapi E, Gavriouchkina D, Senanayake U, Ling ITC, Telenius J, Taylor S, Hughes J, Sauka-Spengler T Abstract Precise control of developmental processes is encoded in the genome in the form of gene regulatory networks (GRNs). Such multi-factorial systems are difficult to decode in vertebrates owing to their complex gene hierarchies and dynamic molecular interactions. Here we present a genome-wide in vivo reconstruction of the GRN unde...
Source: Developmental Cell - October 21, 2019 Category: Cytology Authors: Williams RM, Candido-Ferreira I, Repapi E, Gavriouchkina D, Senanayake U, Ling ITC, Telenius J, Taylor S, Hughes J, Sauka-Spengler T Tags: Dev Cell Source Type: research

MicroRNAs Establish the Right-Handed Dominance of the Heart Laterality Pathway in Vertebrates.
J, Nieto MA Abstract Despite their external bilateral symmetry, vertebrates have internal left/right (L/R) asymmetries required for optimal organ function. BMP-induced epithelial to mesenchymal transition (EMT) in the lateral plate mesoderm (LPM) triggers L/R asymmetric cell movements toward the midline, higher from the right, which are crucial for heart laterality in vertebrates. However, how the L/R asymmetric levels of EMT factors are achieved is not known. Here, we show that the posterior-to-anterior Nodal wave upregulates several microRNAs (miRNAs) to transiently attenuate the levels of EMT factors (Prrx1a an...
Source: Developmental Cell - October 17, 2019 Category: Cytology Authors: Rago L, Castroviejo N, Fazilaty H, Garcia-Asencio F, Ocaña OH, Galcerán J, Nieto MA Tags: Dev Cell Source Type: research

Quantification of Proteins and Histone Marks in Drosophila Embryos Reveals Stoichiometric Relationships Impacting Chromatin Regulation.
ml;ller J Abstract Gene transcription in eukaryotes is regulated through dynamic interactions of a variety of different proteins with DNA in the context of chromatin. Here, we used mass spectrometry for absolute quantification of the nuclear proteome and methyl marks on selected lysine residues in histone H3 during two stages of Drosophila embryogenesis. These analyses provide comprehensive information about the absolute copy number of several thousand proteins and reveal unexpected relationships between the abundance of histone-modifying and -binding proteins and the chromatin landscape that they generate and int...
Source: Developmental Cell - October 16, 2019 Category: Cytology Authors: Bonnet J, Lindeboom RGH, Pokrovsky D, Stricker G, Çelik MH, Rupp RAW, Gagneur J, Vermeulen M, Imhof A, Müller J Tags: Dev Cell Source Type: research

Characterization of Button Loci that Promote Homologous Chromosome Pairing and Cell-Type-Specific Interchromosomal Gene Regulation.
Abstract Homologous chromosomes colocalize to regulate gene expression in processes including genomic imprinting, X-inactivation, and transvection. In Drosophila, homologous chromosomes pair throughout development, promoting transvection. The "button" model of pairing proposes that specific regions along chromosomes pair with high affinity. Here, we identify buttons interspersed across the fly genome that pair with their homologous sequences, even when relocated to multiple positions in the genome. A majority of transgenes that span a full topologically associating domain (TAD) function as butt...
Source: Developmental Cell - October 10, 2019 Category: Cytology Authors: Viets K, Sauria MEG, Chernoff C, Rodriguez Viales R, Echterling M, Anderson C, Tran S, Dove A, Goyal R, Voortman L, Gordus A, Furlong EEM, Taylor J, Johnston RJ Tags: Dev Cell Source Type: research

Maturation of the Human Intestinal Immune System Occurs Early in Fetal Development.
Abstract There are limited data on fetal and early life development of human intestinal immunity. Using mass cytometry (CyTOF) and next-generation sequencing of B and T cell receptor (BCR and TCR) repertoires, we demonstrate complex intestinal immunity from 16 weeks' gestational age (GA). Both BCR and TCR repertoires are diverse with CDRH and CDR3β length increasing with advancing GA. The difference-from-germline, CDR insertions and/or deletions, similarly occur in utero for TCR but not BCR, suggesting earlier mucosal T than B cell maturity. Innate immunity is dominated by macrophages, dendritic cells (D...
Source: Developmental Cell - October 9, 2019 Category: Cytology Authors: Stras SF, Werner L, Toothaker JM, Olaloye OO, Oldham AL, McCourt CC, Lee YN, Rechavi E, Shouval DS, Konnikova L Tags: Dev Cell Source Type: research

Active Fluctuations of the Nuclear Envelope Shape the Transcriptional Dynamics in Oocytes.
Abstract Nucleus position in cells can act as a developmental cue. Mammalian oocytes position their nucleus centrally using an F-actin-mediated pressure gradient. The biological significance of nucleus centering in mammalian oocytes being unknown, we sought to assess the F-actin pressure gradient effect on the nucleus. We addressed this using a dedicated computational 3D imaging approach, biophysical analyses, and a nucleus repositioning assay in mouse oocytes mutant for cytoplasmic F-actin. We found that the cytoplasmic activity, in charge of nucleus centering, shaped the nucleus while promoting nuclear envelope ...
Source: Developmental Cell - October 9, 2019 Category: Cytology Authors: Almonacid M, Al Jord A, El-Hayek S, Othmani A, Coulpier F, Lemoine S, Miyamoto K, Grosse R, Klein C, Piolot T, Mailly P, Voituriez R, Genovesio A, Verlhac MH Tags: Dev Cell Source Type: research

Membrane Tension Orchestrates Rear Retraction in Matrix-Directed Cell Migration.
Abstract In development, wound healing, and cancer metastasis, vertebrate cells move through 3D interstitial matrix, responding to chemical and physical guidance cues. Protrusion at the cell front has been extensively studied, but the retraction phase of the migration cycle is not well understood. Here, we show that fast-moving cells guided by matrix cues establish positive feedback control of rear retraction by sensing membrane tension. We reveal a mechanism of rear retraction in 3D matrix and durotaxis controlled by caveolae, which form in response to low membrane tension at the cell rear. Caveolae activate RhoA...
Source: Developmental Cell - October 9, 2019 Category: Cytology Authors: Hetmanski JHR, de Belly H, Busnelli I, Waring T, Nair RV, Sokleva V, Dobre O, Cameron A, Gauthier N, Lamaze C, Swift J, Campo AD, Starborg T, Zech T, Goetz JG, Paluch EK, Schwartz JM, Caswell PT Tags: Dev Cell Source Type: research

Planar Differential Growth Rates Initiate Precise Fold Positions in Complex Epithelia.
We present a computational model of morphogenesis, encompassing local differential growth and tissue mechanics, to investigate tissue fold positioning. We use the Drosophila wing disc as our model system and show that there is spatial-temporal heterogeneity in its planar growth rates. This differential growth, especially at the early stages of development, is the main driver for fold positioning. Increased apical layer stiffness and confinement by the basement membrane drive fold formation but influence positioning to a lesser degree. The model successfully predicts the in vivo morphology of overgrowth clones and wing...
Source: Developmental Cell - October 8, 2019 Category: Cytology Authors: Tozluoǧlu M, Duda M, Kirkland NJ, Barrientos R, Burden JJ, Muñoz JJ, Mao Y Tags: Dev Cell Source Type: research

Packing in the Proteins.
Abstract In this issue of Developmental Cell, Park et al. (2019) demonstrate that specialized enterocytes of the developing vertebrate intestine are equipped with a broad-spectrum protein absorption machinery to meet animals' nutritional needs through intracellular protein digestion while simultaneously allowing important immune and developmental proteins to traverse the lumen unscathed. PMID: 31593648 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - October 7, 2019 Category: Cytology Authors: Massaquoi MS, Guillemin K Tags: Dev Cell Source Type: research

Sequence and Expression Differences Underlie Functional Specialization of Arabidopsis MicroRNAs miR159 and miR319.
PMID: 31593649 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - October 7, 2019 Category: Cytology Authors: Palatnik JF, Wollmann H, Schommer C, Schwab R, Boisbouvier J, Rodriguez R, Warthmann N, Allen E, Dezulian T, Huson D, Carrington JC, Weigel D Tags: Dev Cell Source Type: research

Epithelial Morphogenesis: Size Matters.
Abstract In this issue of Developmental Cell, Gibson and colleagues (Ramanathan et al., 2019) investigate the relationship between size and shape in epithelial cells. They find that cell size impacts cell shape, with unexpected consequences for epithelial growth and morphogenesis, particularly the clonal dynamics of epithelial cells. PMID: 31593650 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - October 7, 2019 Category: Cytology Authors: Thompson BJ Tags: Dev Cell Source Type: research

Cell Competition Triggers Suicide by Autophagy.
Abstract Cell competition eradicates weaker cells from an epithelium and is important for organ homeostasis. In this issue of Developmental Cell, Nagata et al. (2019) uncover that eradication of loser cells depends on autophagy-mediated cell death. PMID: 31593651 [PubMed - in process] (Source: Developmental Cell)
Source: Developmental Cell - October 7, 2019 Category: Cytology Authors: Dillard C, Rusten TE Tags: Dev Cell Source Type: research

The G2-to-M Transition Is Ensured by a Dual Mechanism that Protects Cyclin B from Degradation by Cdc20-Activated APC/C.
Abstract In the eukaryotic cell cycle, a threshold level of cyclin B accumulation triggers the G2-to-M transition, and subsequent cyclin B destruction triggers mitotic exit. The anaphase-promoting complex/cyclosome (APC/C) is the E3 ubiquitin ligase that, together with its co-activator Cdc20, targets cyclin B for destruction during mitotic exit. Here, we show that two pathways act in concert to protect cyclin B from Cdc20-activated APC/C in G2, in order to enable cyclin B accumulation and the G2-to-M transition. The first pathway involves the Mad1-Mad2 spindle checkpoint complex, acting in a distinct manner from c...
Source: Developmental Cell - October 1, 2019 Category: Cytology Authors: Lara-Gonzalez P, Moyle MW, Budrewicz J, Mendoza-Lopez J, Oegema K, Desai A Tags: Dev Cell Source Type: research

Single-Cell and Population-Level Analyses Using Real-Time Kinetic Labeling Couples Proliferation and Cell Death Mechanisms.
Abstract Quantifying cytostatic and cytotoxic outcomes are integral components of characterizing perturbagens used as research tools and in drug discovery pipelines. Furthermore, data-rich acquisition, coupled with robust methods for analysis, is required to properly assess the function and impact of these perturbagens. Here, we present a detailed and versatile method for single-cell and population-level analyses using real-time kinetic labeling (SPARKL). SPARKL integrates high-content live-cell imaging with automated detection and analysis of fluorescent reporters of cell death. We outline several examples of zer...
Source: Developmental Cell - September 25, 2019 Category: Cytology Authors: Gelles JD, Mohammed JN, Santos LC, Legarda D, Ting AT, Chipuk JE Tags: Dev Cell Source Type: research