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Developmental Cell

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https://www.readbyqxmd.com/read/29337000/mechanical-forces-program-the-orientation-of-cell-division-during-airway-tube-morphogenesis
#1
Zan Tang, Yucheng Hu, Zheng Wang, Kewu Jiang, Cheng Zhan, Wallace F Marshall, Nan Tang
Oriented cell division plays a key role in controlling organogenesis. The mechanisms for regulating division orientation at the whole-organ level are only starting to become understood. By combining 3D time-lapse imaging, mouse genetics, and mathematical modeling, we find that global orientation of cell division is the result of a combination of two types of spindles with distinct spindle dynamic behaviors in the developing airway epithelium. Fixed spindles follow the classic long-axis rule and establish their division orientation before metaphase...
January 9, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29290589/ccpg1-is-a-non-canonical-autophagy-cargo-receptor-essential-for-er-phagy-and-pancreatic-er-proteostasis
#2
Matthew D Smith, Margaret E Harley, Alain J Kemp, Jimi Wills, Martin Lee, Mark Arends, Alex von Kriegsheim, Christian Behrends, Simon Wilkinson
Mechanisms of selective autophagy of the ER, known as ER-phagy, require molecular delineation, particularly in vivo. It is unclear how these events control ER proteostasis and cellular health. Here, we identify cell-cycle progression gene 1 (CCPG1), an ER-resident protein with no known physiological role, as a non-canonical cargo receptor that directly binds to core autophagy proteins via an LIR motif to mammalian ATG8 proteins and, independently and via a discrete motif, to FIP200. These interactions facilitate ER-phagy...
December 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29290588/arabidopsis-argonaute-1-binds-chromatin-to-promote-gene-transcription-in-response-to-hormones-and-stresses
#3
Chang Liu, Ying Xin, Le Xu, Zhaokui Cai, Yuanchao Xue, Yong Liu, Daoxin Xie, Yule Liu, Yijun Qi
Conventional RNA interference (RNAi) pathways suppress eukaryotic gene expression at the transcriptional or post-transcriptional level. At the core of RNAi are small RNAs (sRNAs) and effector Argonaute (AGO) proteins. Arabidopsis AGO1 is known to bind microRNAs (miRNAs) and post-transcriptionally repress target genes in the cytoplasm. Here, we report that AGO1 also binds to the chromatin of active genes and promotes their transcription. We show that sRNAs and SWI/SNF complexes associate with nuclear AGO1 and are required for AGO1 binding to chromatin...
December 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29290587/rapgef5-regulates-nuclear-translocation-of-%C3%AE-catenin
#4
John N Griffin, Florencia Del Viso, Anna R Duncan, Andrew Robson, Woong Hwang, Saurabh Kulkarni, Karen J Liu, Mustafa K Khokha
Canonical Wnt signaling coordinates many critical aspects of embryonic development, while dysregulated Wnt signaling contributes to common diseases, including congenital malformations and cancer. The nuclear localization of β-catenin is the defining step in pathway activation. However, despite intensive investigation, the mechanisms regulating β-catenin nuclear transport remain undefined. In a patient with congenital heart disease and heterotaxy, a disorder of left-right patterning, we previously identified the guanine nucleotide exchange factor, RAPGEF5...
December 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29290586/engineered-tissue-folding-by-mechanical-compaction-of-the-mesenchyme
#5
Alex J Hughes, Hikaru Miyazaki, Maxwell C Coyle, Jesse Zhang, Matthew T Laurie, Daniel Chu, Zuzana Vavrušová, Richard A Schneider, Ophir D Klein, Zev J Gartner
Many tissues fold into complex shapes during development. Controlling this process in vitro would represent an important advance for tissue engineering. We use embryonic tissue explants, finite element modeling, and 3D cell-patterning techniques to show that mechanical compaction of the extracellular matrix during mesenchymal condensation is sufficient to drive tissue folding along programmed trajectories. The process requires cell contractility, generates strains at tissue interfaces, and causes patterns of collagen alignment around and between condensates...
December 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29290585/a-human-ips-model-implicates-embryonic-b-myeloid-fate-restriction-as-developmental-susceptibility-to-b%C3%A2-acute-lymphoblastic-leukemia-associated-etv6-runx1
#6
Charlotta Böiers, Simon E Richardson, Emma Laycock, Alya Zriwil, Virginia A Turati, John Brown, Jason P Wray, Dapeng Wang, Chela James, Javier Herrero, Ewa Sitnicka, Stefan Karlsson, Andrew J H Smith, Sten Erik W Jacobsen, Tariq Enver
ETV6-RUNX1 is associated with childhood acute B-lymphoblastic leukemia (cALL) functioning as a first-hit mutation that initiates a clinically silent pre-leukemia in utero. Because lineage commitment hierarchies differ between embryo and adult, and the impact of oncogenes is cell-context dependent, we hypothesized that the childhood affiliation of ETV6-RUNX1 cALL reflects its origins in a progenitor unique to embryonic life. We characterize the first emerging B cells in first-trimester human embryos, identifying a developmentally restricted CD19-IL-7R+ progenitor compartment, which transitions from a myeloid to lymphoid program during ontogeny...
December 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29290584/crispr-screens-uncover-genes-that-regulate-target-cell-sensitivity-to-the-morphogen-sonic-hedgehog
#7
Ganesh V Pusapati, Jennifer H Kong, Bhaven B Patel, Arunkumar Krishnan, Andreas Sagner, Maia Kinnebrew, James Briscoe, L Aravind, Rajat Rohatgi
To uncover regulatory mechanisms in Hedgehog (Hh) signaling, we conducted genome-wide screens to identify positive and negative pathway components and validated top hits using multiple signaling and differentiation assays in two different cell types. Most positive regulators identified in our screens, including Rab34, Pdcl, and Tubd1, were involved in ciliary functions, confirming the central role for primary cilia in Hh signaling. Negative regulators identified included Megf8, Mgrn1, and an unannotated gene encoding a tetraspanin protein we named Atthog...
December 26, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29290583/lipid-homeostasis-is-maintained-by-dual-targeting-of-the-mitochondrial-pe-biosynthesis-enzyme-to-the-er
#8
Jonathan R Friedman, Muthukumar Kannan, Alexandre Toulmay, Calvin H Jan, Jonathan S Weissman, William A Prinz, Jodi Nunnari
Spatial organization of phospholipid synthesis in eukaryotes is critical for cellular homeostasis. The synthesis of phosphatidylcholine (PC), the most abundant cellular phospholipid, occurs redundantly via the ER-localized Kennedy pathway and a pathway that traverses the ER and mitochondria via membrane contact sites. The basis of the ER-mitochondrial PC synthesis pathway is the exclusive mitochondrial localization of a key pathway enzyme, phosphatidylserine decarboxylase Psd1, which generates phosphatidylethanolamine (PE)...
December 26, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29275993/long-range-signaling-activation-and-local-inhibition-separate-the-mesoderm-and-endoderm-lineages
#9
Antonius L van Boxtel, Andrew D Economou, Claire Heliot, Caroline S Hill
Specification of the three germ layers by graded Nodal signaling has long been seen as a paradigm for patterning through a single morphogen gradient. However, by exploiting the unique properties of the zebrafish embryo to capture the dynamics of signaling and cell fate allocation, we now demonstrate that Nodal functions in an incoherent feedforward loop, together with Fgf, to determine the pattern of endoderm and mesoderm specification. We show that Nodal induces long-range Fgf signaling while simultaneously inducing the cell-autonomous Fgf signaling inhibitor Dusp4 within the first two cell tiers from the margin...
December 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29275992/variation-in-splicing-efficiency-underlies-morphological-evolution-in-capsella
#10
Ushio Fujikura, Runchun Jing, Atsushi Hanada, Yumiko Takebayashi, Hitoshi Sakakibara, Shinjiro Yamaguchi, Christian Kappel, Michael Lenhard
Understanding the molecular basis of morphological change remains a central challenge in evolutionary-developmental biology. The transition from outbreeding to selfing is often associated with a dramatic reduction in reproductive structures and functions, such as the loss of attractive pheromones in hermaphroditic Caenorhabditis elegans and a reduced flower size in plants. Here, we demonstrate that variation in the level of the brassinosteroid-biosynthesis enzyme CYP724A1 contributes to the reduced flower size of selfing Capsella rubella compared with its outbreeding ancestor Capsella grandiflora...
December 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29275994/a-proximity-labeling-strategy-provides-insights-into-the-composition-and-dynamics-of-lipid-droplet-proteomes
#11
Kirill Bersuker, Clark W H Peterson, Milton To, Steffen J Sahl, Victoria Savikhin, Elizabeth A Grossman, Daniel K Nomura, James A Olzmann
Lipid droplet (LD) functions are regulated by a complement of integral and peripheral proteins that associate with the bounding LD phospholipid monolayer. Defining the composition of the LD proteome has remained a challenge due to the presence of contaminating proteins in LD-enriched buoyant fractions. To overcome this limitation, we developed a proximity labeling strategy that exploits LD-targeted APEX2 to biotinylate LD proteins in living cells. Application of this approach to two different cell types identified the vast majority of previously validated LD proteins, excluded common contaminating proteins, and revealed new LD proteins...
December 19, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29275991/phytochrome-a-negatively-regulates-the-shade-avoidance-response-by-increasing-auxin-indole-acidic-acid-protein-stability
#12
Chuanwei Yang, Famin Xie, Yupei Jiang, Zhen Li, Xu Huang, Lin Li
The reduction in the red to far-red light ratio (R/FR) and photosynthetically active radiation caused by dense planting initiates shade avoidance responses (SARs) to help plants compete against their neighbors. However, deep shade attenuates shade-induced stem elongation to suppress excessive reversion toward skotomorphogenic development, in which photoreceptor phytochrome A (PHYA) has been known to play the major role. However, the molecular mechanism underlying PHYA function in deep shade is poorly understood...
December 18, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29249622/differential-expression-of-nf2-in-neuroepithelial-compartments-is-necessary-for-mammalian-eye-development
#13
Kyeong Hwan Moon, Hyoung-Tai Kim, Dahye Lee, Mahesh B Rao, Edward M Levine, Dae-Sik Lim, Jin Woo Kim
The optic neuroepithelial continuum of vertebrate eye develops into three differentially growing compartments: the retina, the ciliary margin (CM), and the retinal pigment epithelium (RPE). Neurofibromin 2 (Nf2) is strongly expressed in slowly expanding RPE and CM compartments, and the loss of mouse Nf2 causes hyperplasia in these compartments, replicating the ocular abnormalities seen in human NF2 patients. The hyperplastic ocular phenotypes were largely suppressed by heterozygous deletion of Yap and Taz, key targets of the Nf2-Hippo signaling pathway...
December 12, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29233477/molecular-anatomy-of-the-developing-human-retina
#14
Akina Hoshino, Rinki Ratnapriya, Matthew J Brooks, Vijender Chaitankar, Matthew S Wilken, Chi Zhang, Margaret R Starostik, Linn Gieser, Anna La Torre, Mario Nishio, Olivia Bates, Ashley Walton, Olivia Bermingham-McDonogh, Ian A Glass, Rachel O L Wong, Anand Swaroop, Thomas A Reh
Clinical and genetic heterogeneity associated with retinal diseases makes stem-cell-based therapies an attractive strategy for personalized medicine. However, we have limited understanding of the timing of key events in the developing human retina, and in particular the factors critical for generating the unique architecture of the fovea and surrounding macula. Here we define three key epochs in the transcriptome dynamics of human retina from fetal day (D) 52 to 136. Coincident histological analyses confirmed the cellular basis of transcriptional changes and highlighted the dramatic acceleration of development in the fovea compared with peripheral retina...
December 1, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29233476/e2f-dp-prevents-cell-cycle-progression-in-endocycling-fat-body-cells-by-suppressing-datm-expression
#15
Ana Guarner, Robert Morris, Michael Korenjak, Myriam Boukhali, Maria Paula Zappia, Capucine Van Rechem, Johnathan R Whetstine, Sridhar Ramaswamy, Lee Zou, Maxim V Frolov, Wilhelm Haas, Nicholas J Dyson
To understand the consequences of the complete elimination of E2F regulation, we profiled the proteome of Drosophila dDP mutants that lack functional E2F/DP complexes. The results uncovered changes in the larval fat body, a differentiated tissue that grows via endocycles. We report an unexpected mechanism of E2F/DP action that promotes quiescence in this tissue. In the fat body, dE2F/dDP limits cell-cycle progression by suppressing DNA damage responses. Loss of dDP upregulates dATM, allowing cells to sense and repair DNA damage and increasing replication of loci that are normally under-replicated in wild-type tissues...
December 1, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29173819/bleb-expansion-in-migrating-cells-depends-on-supply-of-membrane-from-cell-surface-invaginations
#16
Mohammad Goudarzi, Katsiaryna Tarbashevich, Karina Mildner, Isabell Begemann, Jamie Garcia, Azadeh Paksa, Michal Reichman-Fried, Harsha Mahabaleshwar, Heiko Blaser, Johannes Hartwig, Dagmar Zeuschner, Milos Galic, Michel Bagnat, Timo Betz, Erez Raz
Cell migration is essential for morphogenesis, organ formation, and homeostasis, with relevance for clinical conditions. The migration of primordial germ cells (PGCs) is a useful model for studying this process in the context of the developing embryo. Zebrafish PGC migration depends on the formation of cellular protrusions in form of blebs, a type of protrusion found in various cell types. Here we report on the mechanisms allowing the inflation of the membrane during bleb formation. We show that the rapid expansion of the protrusion depends on membrane invaginations that are localized preferentially at the cell front...
November 21, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29173820/orp-mediated-er-contact-with-endocytic-sites-facilitates-actin-polymerization
#17
Javier Encinar Del Dedo, Fatima-Zahra Idrissi, Isabel María Fernandez-Golbano, Patricia Garcia, Elena Rebollo, Marek K Krzyzanowski, Helga Grötsch, Maria Isabel Geli
Oxysterol binding protein-related proteins (ORPs) are conserved lipid binding polypeptides, enriched at ER contacts sites. ORPs promote non-vesicular lipid transport and work as lipid sensors in the context of many cellular tasks, but the determinants of their distinct localization and function are not understood. Here, we demonstrate that the yeast endocytic invaginations associate with the ER and that this association specifically requires the ORPs Osh2 and Osh3, which bridge the endocytic myosin-I Myo5 to the ER integral-membrane VAMP-associated protein (VAP) Scs2...
November 17, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29103956/mtorc1-mediated-inhibition-of-4ebp1-is-essential-for-hedgehog-signaling-driven-translation-and-medulloblastoma
#18
Chang-Chih Wu, Shirui Hou, Brent A Orr, Bryan R Kuo, Yong Ha Youn, Taren Ong, Fanny Roth, Charles G Eberhart, Giles W Robinson, David J Solecki, Makoto M Taketo, Richard J Gilbertson, Martine F Roussel, Young-Goo Han
Mechanistic target of rapamycin (MTOR) cooperates with Hedgehog (HH) signaling, but the underlying mechanisms are incompletely understood. Here we provide genetic, biochemical, and pharmacologic evidence that MTOR complex 1 (mTORC1)-dependent translation is a prerequisite for HH signaling. The genetic loss of mTORC1 function inhibited HH signaling-driven growth of the cerebellum and medulloblastoma. Inhibiting translation or mTORC1 blocked HH signaling. Depleting 4EBP1, an mTORC1 target that inhibits translation, alleviated the dependence of HH signaling on mTORC1...
October 31, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29103952/osteoblast-production-by-reserved-progenitor-cells-in-zebrafish-bone-regeneration-and-maintenance
#19
Kazunori Ando, Eri Shibata, Stefan Hans, Michael Brand, Atsushi Kawakami
Mammals cannot re-form heavily damaged bones as in large fracture gaps, whereas zebrafish efficiently regenerate bones even after amputation of appendages. However, the source of osteoblasts that mediate appendage regeneration is controversial. Several studies in zebrafish have shown that osteoblasts are generated by dedifferentiation of existing osteoblasts at injured sites, but other observations suggest that de novo production of osteoblasts also occurs. In this study, we found from cell-lineage tracing and ablation experiments that a group of cells reserved in niches serves as osteoblast progenitor cells (OPCs) and has a significant role in fin ray regeneration...
October 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29316444/force-generation-via-%C3%AE-cardiac-myosin-titin-and-%C3%AE-actinin-drives-cardiac-sarcomere-assembly-from-cell-matrix-adhesions
#20
Anant Chopra, Matthew L Kutys, Kehan Zhang, William J Polacheck, Calvin C Sheng, Rebeccah J Luu, Jeroen Eyckmans, J Travis Hinson, Jonathan G Seidman, Christine E Seidman, Christopher S Chen
Truncating mutations in the sarcomere protein titin cause dilated cardiomyopathy due to sarcomere insufficiency. However, it remains mechanistically unclear how these mutations decrease sarcomere content in cardiomyocytes. Utilizing human induced pluripotent stem cell-derived cardiomyocytes, CRISPR/Cas9, and live microscopy, we characterize the fundamental mechanisms of human cardiac sarcomere formation. We observe that sarcomerogenesis initiates at protocostameres, sites of cell-extracellular matrix adhesion, where nucleation and centripetal assembly of α-actinin-2-containing fibers provide a template for the fusion of Z-disk precursors, Z bodies, and subsequent striation...
January 8, 2018: Developmental Cell
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