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https://www.readbyqxmd.com/read/29224891/the-bmp-signaling-pathway-regulates-development-of-left-right-asymmetry-in-amphioxus
#1
Vladimir Soukup, Zbynek Kozmik
Establishment of asymmetry along the left-right (LR) body axis in vertebrates requires interplay between Nodal and Bmp signaling pathways. In the basal chordate amphioxus, the left-sided activity of the Nodal signaling has been attributed to the asymmetric morphogenesis of paraxial structures and pharyngeal organs, however the role of Bmp signaling in LR asymmetry establishment has not been addressed to date. Here, we show that Bmp signaling is necessary for the development of LR asymmetric morphogenesis of amphioxus larvae through regulation of Nodal signaling...
December 7, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29215332/nodal-patterning-without-lefty-inhibitory-feedback-is-functional-but-fragile
#2
Katherine W Rogers, Nathan D Lord, James A Gagnon, Andrea Pauli, Steven Zimmerman, Deniz C Aksel, Deepak Reyon, Shengdar Q Tsai, J Keith Joung, Alexander F Schier
Developmental signaling pathways often activate their own inhibitors. Such inhibitory feedback has been suggested to restrict the spatial and temporal extent of signaling or mitigate signaling fluctuations, but these models are difficult to rigorously test. Here, we determine whether the ability of the mesendoderm inducer Nodal to activate its inhibitor Lefty is required for development. We find that zebrafish lefty mutants exhibit excess Nodal signaling and increased specification of mesendoderm, resulting in embryonic lethality...
December 7, 2017: ELife
https://www.readbyqxmd.com/read/29162051/in-vitro-characterization-of-cd133-lo-cancer-stem-cells-in-retinoblastoma-y79-cell-line
#3
Rohini M Nair, Murali Ms Balla, Imran Khan, Ravi Kiran Reddy Kalathur, Paturu Kondaiah, Geeta K Vemuganti
BACKGROUND: Retinoblastoma (Rb), the most common childhood intraocular malignant tumor, is reported to have cancer stem cells (CSCs) similar to other tumors. Our previous investigation in primary tumors identified the small sized cells with low CD133 (Prominin-1) and high CD44 (Hyaluronic acid receptor) expression to be putative Rb CSCs using flow cytometry (FSC(lo)/SSC(lo)/CD133(lo)/CD44(hi)). With this preliminary data, we have now utilized a comprehensive approach of in vitro characterization of Y79 Rb cell line following CSC enrichment using CD133 surface marker and subsequent validation to confirm the functional properties of CSCs...
November 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29122841/hh-gene-participates-in-the-left-right-asymmetry-development-of-amphioxus-by-controlling-cer-expression
#4
Guangwei Hu, Guang Li, Hui Wang, Yiquan Wang
Correct patterning of left-right asymmetry is an important process during the embryonic development of bilaterians. It is known that Hh signaling plays a role in LR asymmetry development of mouse, chicken and sea urchin embryos by regulating Nodal expression. In this study, we reported a novel regulating way of Hh gene in the LR asymmetry development of amphioxus embryos. Our results revealed that Hh-/- embryos abolished Cerburs (Cer) transcription and led to bilaterally symmetric expression of Nodal, Lefty and Pitx As a consequence, Hh-/- mutants duplicated its left-side structures and lost right-side characters displaying an abnormal bilaterally symmetric body plan...
November 9, 2017: Development
https://www.readbyqxmd.com/read/28969018/identification-of-lefty-as-a-molecular-marker-for-ovarian-clear-cell-carcinoma
#5
Masashi Akiya, Masaaki Yamazaki, Toshihide Matsumoto, Yusuke Kawashima, Yasuko Oguri, Sabine Kajita, Daiki Kijima, Risako Chiba, Ako Yokoi, Hiroyuki Takahashi, Yoshio Kodera, Makoto Saegusa
To identify proteins involved in ovarian clear cell carcinoma (OCCCa), shotgun proteomics analysis was applied using formalin-fixed and paraffin-embedded samples of ovarian carcinoma. Analysis of 1521 proteins revealed that 52 were differentially expressed between four OCCCa and 12 non-OCCCa samples. Of the highly expressed proteins in OCCCa, we focused on left-right determination factor (LEFTY), a novel member of the transforming growth factor-β superfamily. In 143 cases of ovarian epithelial carcinoma including 99 OCCCas and 44 non-OCCCas, LEFTY expression at both mRNA and protein levels was significantly higher in OCCCas compared with non-OCCCas, with the mRNA expression of LEFTY1 being predominant compared to that of LEFTY2...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901900/persistence-of-rsv-promotes-proliferation-and-epithelial-mesenchymal-transition-of-bronchial-epithelial-cells-through-nodal-signaling
#6
Zhao Xiang, Zhang Liang, Huang Yanfeng, Kang Leitao
PURPOSE: Nodal may play an important role in the development of cancers. The present study was designed to determine the effects of Nodal induced by respiratory syncytial virus (RSV) infection on the occurrence and development of lung cancer and the underlying mechanisms. METHODOLOGY: After verification of RSV infection by observation of cytopathic effect and indirect immunofluorescence, real-time PCR, Western blot and methylation assays were used to verify the influence of RSV on Nodal expression...
October 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28818840/hcn4-ion-channel-function-is-required-for-early-events-that-regulate-anatomical-left-right-patterning-in-a-nodal-and-lefty-asymmetric-gene-expression-independent-manner
#7
Vaibhav P Pai, Valerie Willocq, Emily J Pitcairn, Joan M Lemire, Jean-François Paré, Nian-Qing Shi, Kelly A McLaughlin, Michael Levin
Laterality is a basic characteristic of all life forms, from single cell organisms to complex plants and animals. For many metazoans, consistent left-right asymmetric patterning is essential for the correct anatomy of internal organs, such as the heart, gut, and brain; disruption of left-right asymmetry patterning leads to an important class of birth defects in human patients. Laterality functions across multiple scales, where early embryonic, subcellular and chiral cytoskeletal events are coupled with asymmetric amplification mechanisms and gene regulatory networks leading to asymmetric physical forces that ultimately result in distinct left and right anatomical organ patterning...
October 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28733544/identification-of-lefty-as-a-molecular-marker-for-ovarian-clear-cell-carcinoma
#8
Masashi Akiya, Masaaki Yamazaki, Toshihide Matsumoto, Yusuke Kawashima, Yasuko Oguri, Sabine Kajita, Daiki Kijima, Risako Chiba, Ako Yokoi, Hiroyuki Takahashi, Yoshio Kodera, Makoto Saegusa
To identify proteins involved in ovarian clear cell carcinoma (OCCCa), shotgun proteomics analysis was applied using formalin-fixed and paraffin-embedded samples of ovarian carcinoma. Analysis of 1521 proteins revealed that 52 were differentially expressed between four OCCCa and 12 non-OCCCa samples. Of the highly expressed proteins in OCCCa, we focused on left-right determination factor (LEFTY), a novel member of the transforming growth factor-β superfamily. In 143 cases of ovarian epithelial carcinoma including 99 OCCCas and 44 non-OCCCas, LEFTY expression at both mRNA and protein levels was significantly higher in OCCCas compared with non-OCCCas, with the mRNA expression of LEFTY1 being predominant compared to that of LEFTY2...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28468864/nodal-signaling-as-a-developmental-therapeutics-target-in-oncology
#9
REVIEW
Aparna Kalyan, Benedito A Carneiro, Sunandana Chandra, Jason Kaplan, Young Kwang Chae, Maria Matsangou, Mary J C Hendrix, Francis Giles
The tumor microenvironment is a vital feature of oncogenesis and tumor progression. There are several parallels between cancer cells and early developmental stem cells, including their plasticity and signaling mechanisms. In early fetal development, Nodal is expressed for endodermal and mesodermal differentiation. This expression has been shown reemerge in the setting of epithelial cancers, such as breast and melanoma. High Nodal expression correlates to an aggressive tumor grade in these malignancies. Nodal signal begins with its interaction with its coreceptor, Cripto-1, leading to activation of Smad2/Smad3 and ultimately downstream transcription and translation...
May 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28407990/mandibular-movements-in-older-people-with-rheumatoid-arthritis
#10
Kelly Machado de Andrade, Bruna Fernandes Moreira Alfenas, Camila Heitor Campos, Renata Cunha Matheus Rodrigues Garcia
OBJECTIVE: The aim of this study was to compare the mandibular movements in older people with and without temporomandibular disorder (TMD) associated with rheumatoid arthritis (RA). STUDY DESIGN: Thirty partially or completely edentulous older adults (65.33 ± 4.7 years) were assigned to 2 groups: (1) with RA and TMD and (2) without RA and TMD. Chewing movements of the jaws during mastication of the test material (Optocal) and the range of mandibular movements were evaluated by using the JT-3-D kinesiographic device before and after new removable prosthesis insertion...
May 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/28320954/cerberus-nodal-lefty-pitx-signaling-cascade-controls-left-right-asymmetry-in-amphioxus
#11
Guang Li, Xian Liu, Chaofan Xing, Huayang Zhang, Sebastian M Shimeld, Yiquan Wang
Many bilaterally symmetrical animals develop genetically programmed left-right asymmetries. In vertebrates, this process is under the control of Nodal signaling, which is restricted to the left side by Nodal antagonists Cerberus and Lefty. Amphioxus, the earliest diverging chordate lineage, has profound left-right asymmetry as a larva. We show that Cerberus, Nodal, Lefty, and their target transcription factor Pitx are sequentially activated in amphioxus embryos. We then address their function by transcription activator-like effector nucleases (TALEN)-based knockout and heat-shock promoter (HSP)-driven overexpression...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28213468/microencapsulation-of-lefty-secreting-engineered-cells-for-pulmonary-fibrosis-therapy-in-mice
#12
Hongge Ma, Shupei Qiao, Zeli Wang, Shuai Geng, Yufang Zhao, Xiaolu Hou, Weiming Tian, Xiongbiao Chen, Lifen Yao
Idiopathic pulmonary fibrosis (IPF) is a progressive disease that causes unremitting deposition of extracellular matrix proteins, thus resulting in distortion of the pulmonary architecture and impaired gas exchange. Associated with high morbidity and mortality, IPF is generally refractory to current pharmacological therapies. Lefty A, a potent inhibitor of transforming growth factor-β signaling, has been shown to have promising antifibrotic ability in vitro for the treatment of renal fibrosis and other potential organ fibroses...
May 1, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28193178/nodal-and-bmp-expression-during-the-transition-to-pentamery-in-the-sea-urchin-heliocidaris-erythrogramma-insights-into-patterning-the-enigmatic-echinoderm-body-plan
#13
Demian Koop, Paula Cisternas, Valerie B Morris, Dario Strbenac, Jean Yee Hwa Yang, Gregory A Wray, Maria Byrne
BACKGROUND: The molecular mechanisms underlying the development of the unusual echinoderm pentameral body plan and their likeness to mechanisms underlying the development of the bilateral plans of other deuterostomes are of interest in tracing body plan evolution. In this first study of the spatial expression of genes associated with Nodal and BMP2/4 signalling during the transition to pentamery in sea urchins, we investigate Heliocidaris erythrogramma, a species that provides access to the developing adult rudiment within days of fertilization...
February 13, 2017: BMC Developmental Biology
https://www.readbyqxmd.com/read/27867768/induced-pluripotent-stem-cells-from-human-hair-follicle-keratinocytes-as-a-potential-source-for-in-vitro-hair-follicle-cloning
#14
Sheng Jye Lim, Shu Cheow Ho, Pooi Ling Mok, Kian Lee Tan, Alan H K Ong, Seng Chiew Gan
BACKGROUND: Human hair follicles are important for the renewal of new hairs and their development. The generation of induced pluripotent stem cells (iPSCs) from hair follicles is easy due to its accessibility and availability. The pluripotent cells derived from hair follicles not only have a higher tendency to re-differentiate into hair follicles, but are also more suited for growth in hair scalp tissue microenvironment. METHODS: In this study, human hair follicular keratinocytes were used to generate iPSCs, which were then further differentiated in vitro into keratinocytes...
2016: PeerJ
https://www.readbyqxmd.com/read/27760115/tet-mediated-dna-demethylation-controls-gastrulation-by-regulating-lefty-nodal-signalling
#15
Hai-Qiang Dai, Bang-An Wang, Lu Yang, Jia-Jia Chen, Guo-Chun Zhu, Mei-Ling Sun, Hao Ge, Rui Wang, Deborah L Chapman, Fuchou Tang, Xin Sun, Guo-Liang Xu
Mammalian genomes undergo epigenetic modifications, including cytosine methylation by DNA methyltransferases (DNMTs). Oxidation of 5-methylcytosine by the Ten-eleven translocation (TET) family of dioxygenases can lead to demethylation. Although cytosine methylation has key roles in several processes such as genomic imprinting and X-chromosome inactivation, the functional significance of cytosine methylation and demethylation in mouse embryogenesis remains to be fully determined. Here we show that inactivation of all three Tet genes in mice leads to gastrulation phenotypes, including primitive streak patterning defects in association with impaired maturation of axial mesoderm and failed specification of paraxial mesoderm, mimicking phenotypes in embryos with gain-of-function Nodal signalling...
October 27, 2016: Nature
https://www.readbyqxmd.com/read/27554431/lefty-glycoproteins-in-human-embryonic-stem-cells-extracellular-delivery-route-and-posttranslational-modification-in-differentiation
#16
Zhila Khalkhali-Ellis, Vasiliy Galat, Yekaterina Galat, Alina Gilgur, Elisabeth A Seftor, Mary J C Hendrix
Lefty is a member of transforming growth factor-beta (TGF-β) superfamily and a potent antagonist of the TGF-β/Nodal/Activin signaling pathway. Lefty is critical in sustaining self-renewal/pluripotency status, and implicated in the differentiation of embryonic stem cells (ESCs). However, emerging studies depict Lefty as a multifaceted protein involved in myriad cellular events. Lefty proteins (human Lefty A and B) are secreted glycoproteins, but their mode of secretion and the significance of their "glycan" moiety remain mostly unexplored...
September 19, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27488374/nodal-signalling-in-xenopus-the-role-of-xnr5-in-left-right-asymmetry-and-heart-development
#17
Emmanuel Tadjuidje, Matthew Kofron, Adnan Mir, Christopher Wylie, Janet Heasman, Sang-Wook Cha
Nodal class TGF-β signalling molecules play essential roles in establishing the vertebrate body plan. In all vertebrates, nodal family members have specific waves of expression required for tissue specification and axis formation. In Xenopus laevis, six nodal genes are expressed before gastrulation, raising the question of whether they have specific roles or act redundantly with each other. Here, we examine the role of Xnr5. We find it acts at the late blastula stage as a mesoderm inducer and repressor of ectodermal gene expression, a role it shares with Vg1...
August 2016: Open Biology
https://www.readbyqxmd.com/read/27307516/acquisition-of-the-dorsal-structures-in-chordate-amphioxus
#18
Arseniy R Morov, Tharcisse Ukizintambara, Rushan M Sabirov, Kinya Yasui
Acquisition of dorsal structures, such as notochord and hollow nerve cord, is likely to have had a profound influence upon vertebrate evolution. Dorsal formation in chordate development thus has been intensively studied in vertebrates and ascidians. However, the present understanding does not explain how chordates acquired dorsal structures. Here we show that amphioxus retains a key clue to answer this question. In amphioxus embryos, maternal nodal mRNA distributes asymmetrically in accordance with the remodelling of the cortical cytoskeleton in the fertilized egg, and subsequently lefty is first expressed in a patch of blastomeres across the equator where wnt8 is expressed circularly and which will become the margin of the blastopore...
June 2016: Open Biology
https://www.readbyqxmd.com/read/27305836/pierce1-is-critical-for-specification-of-left-right-asymmetry-in-mice
#19
Young Hoon Sung, In-Jeoung Baek, Yong Hwan Kim, Yong Song Gho, S Paul Oh, Young Jae Lee, Han-Woong Lee
The specification of left-right asymmetry of the visceral organs is precisely regulated. The earliest breakage of left-right symmetry occurs as the result of leftward flow generated by asymmetric beating of nodal cilia, which eventually induces asymmetric Nodal/Lefty/Pitx2 expression on the left side of the lateral plate mesoderm. PIERCE1 has been identified as a p53 target gene involved in the DNA damage response. In this study, we found that Pierce1-null mice exhibit severe laterality defects, including situs inversus totalis and heterotaxy with randomized situs and left and right isomerisms...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27293372/stage-specific-differentiation-of-ipscs-toward-retinal-ganglion-cell-lineage
#20
Fei Deng, Mengfei Chen, Ying Liu, Huiling Hu, Yunfan Xiong, Chaochao Xu, Yuchun Liu, Kangjun Li, Jing Zhuang, Jian Ge
PURPOSE: As an alternative and desirable approach for regenerative medicine, human induced pluripotent stem cell (hiPSC) technology raises the possibility of developing patient-tailored cell therapies to treat intractable degenerative diseases in the future. This study was undertaken to guide human Tenon's capsule fibroblasts-derived iPSCs (TiPSCs) to differentiate along the retinal ganglion cell (RGC) lineage, aiming at producing appropriate cellular material for RGC regeneration. METHODS: By mimicking RGC genesis, we deliberately administered the whole differentiation process and directed the stage-specific differentiation of human TiPSCs toward an RGC fate via manipulation of the retinal inducers (DKK1+Noggin+Lefty A) alongside master gene (Atoh7) sequentially...
2016: Molecular Vision
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