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Current Opinion in Genetics & Development

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https://read.qxmd.com/read/31419725/renal-ciliopathies
#1
REVIEW
Laura A Devlin, John A Sayer
Renal ciliopathies are a group of disorders characterised by nephronophthisis, cystic kidneys or renal cystic dysplasia whose underlying disease pathogenesis is related to abnormal structure or function of the primary cilia complex. The number of renal ciliopathies continues to expand as genomic and genetic approaches identify novel causes. This in turn provides new opportunities to explore disease mechanisms and therapeutic approaches to target cystic kidney disease and other associated phenotypes. Here we review recent advances in the field of renal ciliopathies and how these allow new insights into this fascinating spectrum of diseases...
August 13, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31404788/sticking-to-a-plan-adhesion-and-signaling-control-spatial-organization-of-cells-within-migrating-collectives
#2
REVIEW
Frank Macabenta, Angelike Stathopoulos
Collective cell migration is required in a vast array of biological phenomena, including organogenesis and embryonic development. The mechanisms that underlie collective cell migration not only involve the morphogenetic changes associated with single cell migration, but also require the maintenance of cell-cell junctions during movement. Additionally, cell shape changes and polarity must be coordinated in a multicellular manner in order to preserve directional movement in the migrating cohort, and often relates to multiple functions of common signaling pathways...
August 9, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31404787/cytonemes-in-development
#3
REVIEW
Chengting Zhang, Steffen Scholpp
Cell-cell communication is essential during the development of multicellular organisms. Specialized cell protrusions called cytonemes have been identified to exchange signals between cells that are vital for tissue development. Cytonemes can carry signalling components between distant cells and thus regulate the activity levels of the corresponding signalling pathways across entire tissues. This review summarizes the key findings on the formation and function of cytonemes in tissue development.
August 9, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31394307/genome-organization-around-nuclear-speckles
#4
REVIEW
Yu Chen, Andrew S Belmont
Higher eukaryotic cell nuclei are highly compartmentalized into bodies and structural assemblies of specialized functions. Nuclear speckles/IGCs are one of the most prominent nuclear bodies, yet their functional significance remains largely unknown. Recent advances in sequence-based mapping of nuclear genome organization now provide genome-wide analysis of chromosome organization relative to nuclear speckles. Here we review older microscopy-based studies on a small number of genes with the new genomic mapping data suggesting a significant fraction of the genome is almost deterministically positioned near nuclear speckles...
August 5, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31331805/editorial-overview-functionalizing-cancer-genomes-in-the-era-of-big-data
#5
EDITORIAL
Roland Rad, Michael Boutros
No abstract text is available yet for this article.
July 19, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31326647/talpid3-in-joubert-syndrome-and-related-ciliopathy-disorders
#6
REVIEW
Amy M Fraser, Megan G Davey
TALPID3 (KIAA0586) is a centrosomal protein which has specific functions during centriole maturation during the formation of the centrosomal-dependent organelle, the cilia, as well as less well understood roles in the cytoskeleton and during cell polarisation. Cilia are an essential component of signal transduction during embryonic development and the loss of TALPID3 function in humans can cause both severe lethal and mild cilia-related developmental disorders known as 'ciliopathies' the most common being Joubert syndrome...
July 18, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31323466/chromatin-folding-and-nuclear-architecture-prc1-function-in-3d
#7
REVIEW
Robert S Illingworth
Embryonic development requires the intricate balance between the expansion and specialisation of defined cell types in time and space. The gene expression programmes that underpin this balance are regulated, in part, by modulating the chemical and structural state of chromatin. Polycomb repressive complexes (PRCs), a family of essential developmental regulators, operate at this level to stabilise or perpetuate a repressed but transcriptionally poised chromatin configuration. This dynamic state is required to control the timely initiation of productive gene transcription during embryonic development...
July 16, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31323465/disentangling-chromatin-architecture-to-gain-insights-into-the-etiology-of-brain-disorders
#8
REVIEW
Janine M Lamonica, Zhaolan Zhou
Chromatin organization, together with DNA and histone modifications, is directly linked to the spatiotemporal control of gene expression that specifies and maintains cell type-specific functions. This is particularly important in the brain where hundreds of cell types with distinct functions reside. Recent advances in molecular and computational technologies have enabled the query of chromatin architecture at unprecedented resolution and detail. Here, we review recent studies on the emerging importance of chromatin architecture in the pathogenesis of brain disorders, with emphasis on schizophrenia, autism spectrum disorders (ASD), and unstable repeat expansion disorders...
July 16, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31306988/integrating-chemical-and-mechanical-signals-in-neural-crest-cell-migration
#9
REVIEW
Adam Shellard, Roberto Mayor
Neural crest cells are a multipotent embryonic stem cell population that migrate large distances to contribute a variety of tissues. The cranial neural crest, which contribute to tissues of the face and skull, undergo collective migration whose movement has been likened to cancer metastasis. Over the last few years, a variety of mechanisms for the guidance of collective cranial neural crest cell migration have been described: mostly chemical, but more recently mechanical. Here we review these different mechanisms and attempt to integrate them to provide a unified model of collective cranial neural crest cell migration...
July 12, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31306886/biophysical-regulation-of-local-chromatin-structure
#10
REVIEW
Nick Gilbert
DNA in higher eukaryotes is packaged with histone proteins to form nucleosomes which are further assembled into higher-order chromatin fibres to protect and regulate access to the genetic information. Chromatin folding above the nucleosomal level is controversial with differing views proposing unfolded irregular structures through to highly organised chromatin fibres. Using a combination of techniques including sedimentation studies, electron microscopy and superresolution imaging views are converging to indicate that local chromatin is organised into a fibre, peppered with numerous discontinuities and points of flexibility...
July 12, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31306885/implications-of-liquid-liquid-phase-separation-in-plant-chromatin-organization-and-transcriptional-control
#11
REVIEW
Nan Wang, Chang Liu
As an essential feature of three-dimensional (3D) genome organization, compartmentalization of chromatin in the nucleus is tightly linked to various chromatin activities. Recent work on liquid-liquid phase separation (LLPS), which drives the formation of miscellaneous membrane-less compartments in cells, suggests that it is a critical aspect of chromatin compartmentalization. In this review, we provide an overview of recent work in the animal field that focuses on understanding how LLPS is involved in 3D chromatin organization and transcriptional regulation...
July 12, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31302472/redox-regulation-of-development-and-regeneration
#12
REVIEW
James A Coffman, Yi-Hsien Su
Oxygen is essential to contemporary life, providing the major electron sink underlying cellular energy metabolism. In addition to providing energy, largely involving redox reactions within mitochondria, oxidative metabolism produces reactive byproducts that are damaging to cellular components. Eukaryotic organisms have evolved multiple physiological mechanisms and signaling pathways to deal with fluctuating levels of oxygen and reactive oxygen species (ROS), and many of these are used in animals to regulate developmental processes...
July 11, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31302471/inherency-and-homomorphy-in-the-evolution-of-development
#13
REVIEW
Stuart A Newman
Organismal development occurs when expression of certain genes leads to the mobilization of physical forces and effects that shape and pattern multicellular clusters. All materials exhibit preferred forms, but the inherent morphological motifs of some, such as liquids and crystalline solids are well-characterized. Recent work has shown that the origin of the animals (Metazoa) was accompanied by the acquisition by their developing tissues of liquid-like and liquid-crystalline properties. This and the novel capacity to produce stiff internal substrata (basal laminae) set these organisms apart from their closest relatives by the propensity (predictable from their material nature) to form complex bodies and organs...
July 11, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31288129/mapping-the-protein-protein-and-genetic-interactions-of-cancer-to-guide-precision-medicine
#14
REVIEW
Mehdi Bouhaddou, Manon Eckhardt, Zun Zar Chi Naing, Minkyu Kim, Trey Ideker, Nevan J Krogan
Massive efforts to sequence cancer genomes have compiled an impressive catalogue of cancer mutations, revealing the recurrent exploitation of a handful of 'hallmark cancer pathways'. However, unraveling how sets of mutated proteins in these and other pathways hijack pro-proliferative signaling networks and dictate therapeutic responsiveness remains challenging. Here, we show that cancer driver protein-protein interactions are enriched for additional cancer drivers, highlighting the power of physical interaction maps to explain known, as well as uncover new, disease-promoting pathway interrelationships...
July 6, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31260874/the-photoreceptor-cilium-and-its-diseases
#15
REVIEW
Ruxandra Bachmann-Gagescu, Stephan Cf Neuhauss
Light sensation occurs in photoreceptor outer segments (OS), which derive from highly specialized primary cilia, based on structural and molecular similarities. Ciliary dysfunction causes ciliopathies, in which retinal degeneration is common. The connecting cilium (CC) is the obligate passage for proteins moving between ciliary and cellular compartment, controlling the correct distribution of proteins on either side of its barrier. While new mechanisms for selective entry of ciliary proteins are being elucidated, active transport out of the OS is increasingly studied...
June 27, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31234044/genes-and-mechanisms-of-heterotaxy-patients-drive-the-search
#16
REVIEW
Emily Sempou, Mustafa K Khokha
Heterotaxy, a disorder in which visceral organs, including the heart, are mispatterned along the left-right body axis, contributes to particularly severe forms of congenital heart disease that are difficult to mitigate even despite surgical advances. A higher incidence of heterotaxy among individuals with blood kinship and the existence of rare monogenic disease forms suggest the existence of a genetic component, but the genetic and phenotypic heterogeneity of the disease have rendered gene discovery challenging...
June 21, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31201996/cilia-and-development
#17
REVIEW
Vrinda Sreekumar, Dominic P Norris
The role of mammalian cilia in cell signalling was first identified in embryonic development and subsequent analysis has revealed roles in multiple signalling pathways. We now understand that these developmental roles impact human health and this is evident in the class of ciliary diseases which we call the ciliopathies. By their nature cilia defects are usually pleiotropic, affecting more than one system. This often leads to early lethality, meaning that subsequent functions are harder to examine. Current studies are revealing previously unrealised cilia-related phenotypes later in embryonic development...
June 12, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31200172/large-scale-datasets-uncovering-cell-signalling-networks-in-cancer-context-matters
#18
REVIEW
Sumana Sharma, Evangelia Petsalaki
Cell signaling pathways control the responses of cells to external perturbations. Depending on the cell's internal state, genetic background and environmental context, signaling pathways rewire to elicit the appropriate response. Such rewiring also can lead to cancer development and progression or cause resistance to therapies. While there exist static maps of annotated pathways, they do not capture these rewired networks. As large-scale datasets across multiple contexts and patients are becoming available the doors to infer and study context-specific signaling network have also opened...
June 11, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31185381/mechanical-strain-novel-genes-and-evolutionary-insights-news-from-the-frog-left-right-organizer
#19
REVIEW
Martin Blum, Tim Ott
Animal asymmetries are widespread, from lobster claws to human handedness. Controlled by the left-sided Nodal signaling cascade, asymmetric morphogenesis and placement of vertebrate organs (heart, gut, etc.) are executed during embryogenesis. Fish, amphibians and mammals use a ciliated epithelium to break bilateral symmetry and induce the Nodal cascade. Cilia tilt and polarize to the posterior cell pole, such that clockwise rotation causes a leftward flow at the cell surface. Recent progress in Xenopus showed that mechanical strain drives cilia lengthening and polarization...
June 7, 2019: Current Opinion in Genetics & Development
https://read.qxmd.com/read/31128483/genome-activation-and-architecture-in-the-early-mammalian-embryo
#20
REVIEW
Natasha Jansz, Maria-Elena Torres-Padilla
Over the last decade, our understanding of how the genome is packaged in three dimension within the nucleus has grown considerably. This is largely due to advances in high-throughput genomics assays to study higher order chromatin organization. Our knowledge of the structures adopted by the chromatin has far preceded our understanding of function and mechanism. An outstanding question has been how are such structures established. Recently, a suite of genomics assays has been adapted for low-input material, making it possible to apply them to the pre-implantation mammalian embryo...
May 22, 2019: Current Opinion in Genetics & Development
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