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Embryonic lethal

Ivan Lobov, Natalia Mikhailova
Background: Retina is the highest oxygen-demanding and vascularized tissue in the body. Retinal development and function require proper vascularization and blood vessel function and integrity. Dll4 is most prominently expressed in the endothelium of angiogenic blood vessels and in quiescent arteries and capillaries in all tissues and organs of the mammalian species, and it is the key regulator of blood vessel sprouting. Results: Dll4 is a transmembrane protein that acts as a ligand for Notch receptors 1 and 4...
2018: Journal of Ophthalmology
Tie-Gang Meng, Xukun Lu, Lei Guo, Guan-Mei Hou, Xue-Shan Ma, Qian-Nan Li, Lin Huang, Li-Hua Fan, Zheng-Hui Zhao, Xiang-Hong Ou, Ying-Chun OuYang, Heide Schatten, Lei Li, Zhen-Bo Wang, Qing-Yuan Sun
N6-methyladenosine (m6 A) is the most prevalent and reversible internal modification of mammalian messenger and noncoding RNAs mediated by specific m6 A writer, reader, and eraser proteins. As an m6 A writer, the methyltransferase-like 3-methyltransferase-like 14 (METTL14)-Wilms tumor 1-associated protein complex dynamically regulates m6 A modification and plays important roles in diverse biologic processes. However, our knowledge about the complete functions of this RNA methyltransferase complex, the contributions of each component to the methylation, and their effects on different biologic pathways are still limited...
August 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
A E Blanco, D Cavero, W Icken, M Voss, M Schmutz, R Preisinger, A R Sharifi
Selection to reduce susceptibility to Enterococcus faecalis infection in laying hens may contribute to the prevention of amyloid arthropathy since it is mainly induced by this bacterium. Therefore, the aim of the present study was to investigate the possibility to select more laying hens that are resistant against E. faecalis infection through the embryo lethality assay (ELA), which is proposed as an alternative model to replace the adult avian challenge assay. Ten-day-old embryos of 500 Lohmann Brown layers were inoculated into the allantoic cavity with an infectious dose of 2...
August 11, 2018: Poultry Science
Toshiyuki Tsunoda, Keiko Doi, Shuhei Ishikura, Hao Luo, Kensuke Nishi, Hiroshi Matsuzaki, Midori Koyanagi, Yoko Tanaka, Tadashi Okamura, Senji Shirasawa
Zinc finger and AT‑hook domain containing (Zfat) is a transcriptional regulator harboring an AT‑hook domain and 18 repeats of a C2H2 zinc‑finger motif, which binds directly to the proximal region of transcription start sites in Zfat‑target genes. It was previously reported that deletion of the Zfat gene in mice yields embryonic lethality by embryonic day 8.5 and impairs primitive hematopoiesis in yolk sac blood islands. In addition, Zfat has been reported to be involved in thymic T‑cell development and peripheral T‑cell homeostasis...
August 3, 2018: International Journal of Molecular Medicine
Zhongjie Zhang, Baolong Niu, Dongfeng Ji, Muwang Li, Kai Li, Anthony A James, Anjiang Tan, Yongping Huang
Sex separation methods are critical for genetic sexing systems in commercial insect production and sterile insect techniques. Integration of selectable marker genes into a sex chromosome is particularly useful in insects with a heterogametic sex determination system. Here, we describe targeted gene integration of fluorescent marker expression cassettes into a randomly amplified polymorphic DNA (RAPD) marker region in the W chromosome of the lepidopteran model insect Bombyx mori using transcriptional activator-like effector nuclease (TALEN)-mediated genome editing...
August 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
Goldie Y L Lui, Carla Grandori, Christopher J Kemp
Cyclin-dependent kinase 12 (CDK12) belongs to the cyclin-dependent kinase (CDK) family of serine/threonine protein kinases that regulate transcriptional and post-transcriptional processes, thereby modulating multiple cellular functions. Early studies characterised CDK12 as a transcriptional CDK that complexes with cyclin K to mediate gene transcription by phosphorylating RNA polymerase II. CDK12 has been demonstrated to specifically upregulate the expression of genes involved in response to DNA damage, stress and heat shock...
August 13, 2018: Journal of Clinical Pathology
Javier Conde-Vancells, Mercedes Vazquez-Chantada, Catherine W McCollum, Maria Bondesson, Sharanya Maanasi Kalasekar, Bogdan J Wlodarczyk, Jan-Åke Gustafsson, Robert M Cabrera, Richard H Finnell
In this study we combine assays using mouse embryonic stem cells (mESCs) and zebrafish embryos to evaluate the potential developmental toxicity of industrial and pharmaceutical chemicals. A set of eleven chemicals of known mammalian in vivo teratogenicity were tested in the assays and correlations to mammalian data investigated. Using mESCs, proliferation, differentiation, and cytotoxicity of the chemicals were measured. In zebrafish embryos, lethality and the lowest effect level concentrations for morphological malformations were determined...
August 10, 2018: Reproductive Toxicology
Rhys Cartlidge, Donald Wlodkowic
An increased interest in implementations of Lab-on-a-Chip (LOC) technologies for in-situ analysis of multicellular metazoan model organisms and their embryonic stages demands development of new prototyping techniques. Due to size of multicellular organisms the fabrication of soft-lithography molds requires features with high aspect ratios as well as deposition of layers with significant thicknesses. This makes them time consuming and difficult to fabricate using conventional photolithography techniques. In this work we describe development of a rapid technique capable of generating thick films achieved with high viscosity SU-8 and used in fabricating master templates for high aspect ratio micro- and mesofluidic devices...
August 13, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Yubing Liu, Wei Zou, Peiguo Yang, Li Wang, Yan Ma, Hong Zhang, Xiaochen Wang
Ribosome degradation through the autophagy-lysosome pathway is crucial for cell survival during nutrient starvation, but whether it occurs under normal growth conditions and contributes to animal physiology remains unaddressed. In this study, we identified RNST-2, a C. elegans T2 family endoribonuclease, as the key enzyme that degrades ribosomal RNA in lysosomes. We found that loss of rnst-2 causes accumulation of rRNA and ribosomal proteins in enlarged lysosomes and both phenotypes are suppressed by blocking autophagy, which indicates that RNST-2 mediates autophagic degradation of ribosomal RNA in lysosomes...
August 13, 2018: ELife
Bo Wang, Guting Liu, Jing Zhang, Yuan Li, Hailian Yang, Dongtao Ren
In Arabidopsis, embryonic development follows a stereotypical pattern of cell division. Although many factors have been reported to participate in the proper embryonic pattern establishment, the molecular mechanisms underlying the pattern formation are unclear. In this study, we showed that RAF22 and RAF28, two RAF-like MAPKKKs in Arabidopsis, are involved in the regulation of embryogenesis. The double knockout mutant of RAF22 and RAF28 was embryonic lethal. A large proportion of the raf22-/- raf28+/- mutant embryos exhibited various defects, including disordered proembryo cell divisions, disruption of the bilaterally symmetrical structure, abnormally formative divisions of hypophysis and exaggerated suspensor growth...
August 12, 2018: Plant Journal: for Cell and Molecular Biology
Lyndsay A Wylie, Kevin P Mouillesseaux, Diana C Chong, Victoria L Bautch
The BMP pathway regulates developmental processes including angiogenesis, yet its signaling outputs are complex and context-dependent. Recently, we showed that SMAD6, an intracellular BMP inhibitor expressed in endothelial cells, decreases vessel sprouting and branching both in vitro and in zebrafish. Genetic deletion of SMAD6 in mice results in poorly characterized cardiovascular defects and lethality. Here, we analyzed the effects of SMAD6 loss on vascular function during murine development. SMAD6 was expressed in a subset of blood vessels throughout development, primarily in arteries, while expression outside of the vasculature was largely confined to developing cardiac valves with no obvious embryonic phenotype...
August 9, 2018: Developmental Biology
Aaron B Bogutz, Rosemary Oh-McGinnis, Karen J Jacob, Rita Ho-Lau, Ting Gu, Marina Gertsenstein, Andras Nagy, Louis Lefebvre
The basic helix-loop-helix (bHLH) transcription factor ASCL2 plays essential roles in diploid multipotent trophoblast progenitors, intestinal stem cells, follicular T-helper cells, as well as during epidermal development and myogenesis. During early development, Ascl2 expression is regulated by genomic imprinting and only the maternally inherited allele is transcriptionally active in trophoblast. The paternal allele-specific silencing of Ascl2 requires expression of the long non-coding RNA Kcnq1ot1 in cis and the deposition of repressive histone marks...
August 10, 2018: PLoS Genetics
Jingbo Dai, Qiyuan Zhou, Haiyang Tang, Tianji Chen, Jing Li, Pradip Raychaudhuri, Jason X-J Yuan, Guofei Zhou
RATIONALE: Forkhead box M1 (FoxM1) is a transcription factor that promotes cell proliferation by regulating a broad spectrum of genes that participate in cell cycle regulation, such as Cyclin B, CDC25B, and Aurora B Kinase. We have shown that hypoxia, a well-known stimulus for pulmonary hypertension (PH), induces FoxM1 in pulmonary artery smooth muscle cells (PASMC) in a HIF-dependent pathway, resulting in PASMC proliferation, while the suppression of FoxM1 prevents hypoxia-induced PASMC proliferation...
August 6, 2018: Cellular Signalling
Barbara Dupret, Pamela Völkel, Pauline Follet, Xuefen Le Bourhis, Pierre-Olivier Angrand
Zebrafish is a powerful animal model used to study vertebrate embryogenesis, organ development and diseases (Gut et al., 2017) [1]. The usefulness of the model was established as a result of various large forward genetic screens identifying mutants in almost every organ or cell type (Driever et al., 1996; Haffter et al., 1996) [[2], [3]]. More recently, the advent of genome editing methodologies, including TALENs (Sander et al., 2011) [4] and the CRISPR/Cas9 technology (Hwang et al., 2013) [5], led to an increase in the production of zebrafish mutants...
2018: MethodsX
Daichi Sadato, Tomio Ono, Saki Gotoh-Saito, Naoki Kajiwara, Namiko Nomura, Masako Ukaji, Liying Yang, Kenji Sakimura, Youichi Tajima, Keisuke Oboki, Futoshi Shibasaki
Mammalian eukaryotic translation initiation factor 3 (eIF3) is the largest complex of the translation initiation factors. The eIF3 complex is comprised of thirteen subunits, which are named eIF3a to eIF3 m in most multicellular organisms. The eIF3e gene locus is one of the most frequent integration sites of mouse mammary tumor virus (MMTV), which induces mammary tumors in mice. MMTV-integration events result in the expression of C-terminal-truncated eIF3e proteins, leading to mammary tumor formation. We have shown that tumor formation can be partly caused by activation of hypoxia-inducible factor 2α...
August 2018: FEBS Open Bio
Maarten M G van den Hoogenhof, Ingeborg van der Made, Nina E de Groot, Amin Damanafshan, Shirley C M van Amersfoorth, Lorena Zentilin, Mauro Giacca, Yigal M Pinto, Esther E Creemers
The RNA-binding protein Rbm24 has recently been identified as a pivotal splicing factor in the developing heart. Loss of Rbm24 in mice disrupts cardiac development by governing a large number of muscle-specific splicing events. Since Rbm24 knockout mice are embryonically lethal, the role of Rbm24 in the adult heart remained unexplored. Here, we used adeno-associated viruses (AAV9) to investigate the effect of increased Rbm24 levels in adult mouse heart. Using high-resolution microarrays, we found 893 differentially expressed genes and 1102 differential splicing events in 714 genes in hearts overexpressing Rbm24...
August 3, 2018: Scientific Reports
Karina N Dubé, Nicola Smart
Formation of the vasculature is a complex process, defects in which can lead to embryonic lethality or disease in later life. Understanding mechanisms of vasculogenesis may facilitate the treatment of developmental defects and may be extrapolated to promote wound healing and tissue repair. Thymosin β4 (Tβ4) is an actin monomer binding protein with recognized roles in vascular development, neovascularization and protection against disease. Areas covered: Vascular network assembly is complex, regulated by multiple signals and cell types; Tβ4 functions in many of the underlying processes, including vasculogenesis, angiogenesis, arteriogenesis, endothelial-mesenchymal transition and extracellular matrix remodeling...
July 2018: Expert Opinion on Biological Therapy
Xiaotong Wu, Weimin Shen, Bingjie Zhang, Anming Meng
Oocytes, the irreplaceable gametes for generating a new organism, are matured in the ovary of living female animals. It is unknown whether any genetic manipulations can be applied to immature oocytes inside the living ovaries. As a proof-of-concept, we here demonstrate genetic amendments of zebrafish immature oocytes within the ovary. Oocyte microinjection in situ (OMIS) stimulates tissue repair responses, but some of microinjected immature oocytes are matured, ovulated and fertilizable. By OMIS-mediated Cas9 approach, ntla and gata5 loci of oocytes arrested at prophase I of meiosis are successfully edited before fertilization...
July 28, 2018: Journal of Molecular Cell Biology
Colin C Conine, Fengyun Sun, Lina Song, Jaime A Rivera-Pérez, Oliver J Rando
The small RNA payload of mammalian sperm undergoes dramatic remodeling during development, as several waves of microRNAs and tRNA fragments are shipped to sperm during post-testicular maturation in the epididymis. Here, we take advantage of this developmental process to probe the function of the sperm RNA payload in preimplantation development. We generated zygotes via intracytoplasmic sperm injection (ICSI) using sperm obtained from the proximal (caput) versus distal (cauda) epididymis and then characterized the development of the resulting embryos...
July 16, 2018: Developmental Cell
Hanadi A Abdelrahman, Aisha Al-Shamsi, Anne John, Jozef Hertecant, Ali Lootah, Bassam R Ali, Lihadh Al-Gazali
Non-immune hydrops fetalis (NIHF) is the abnormal accumulation of serous fluid in more than two fetal or neonatal interstitial spaces due to nonimmune causes. It is a serious condition that requires extensive medical care as it indicates severe fetal compromise. We clinically evaluated four patients from two branches of a highly consanguineous family from the UAE with NIHF using whole exome sequencing and in silico analysis. Fetal onset pleural and peritoneal effusions were detected in all four patients and were born with moderate to severe hydrops fetalis that resolved with age...
July 28, 2018: American Journal of Medical Genetics. Part A
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