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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
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
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
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
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
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
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
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
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
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
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
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
Yin Wang, Xi Wang, Thorsten Wohland, Karuna Sampath
The correct distribution and activity of secreted signaling proteins called morphogens is required for many developmental processes. Nodal morphogens play critical roles in embryonic axis formation in many organisms. Models proposed to generate the Nodal gradient include diffusivity, ligand processing, and a temporal activation window. But how the Nodal morphogen gradient forms in vivo remains unclear. Here, we have measured in vivo for the first time, the binding affinity of Nodal ligands to their major cell surface receptor, Acvr2b, and to the Nodal inhibitor, Lefty, by fluorescence cross-correlation spectroscopy...
2016: ELife
P T Del Giudice, L B Belardin, M Camargo, D S Zylbersztejn, V M Carvalho, K H M Cardozo, R P Bertolla, A P Cedenho
The goal of this study was to determine seminal plasma biomarkers of testicular function in adolescents with varicocoele and to verify enriched gene ontology terms associated to these differential proteomes. An observational study was carried out in an academic research environment. A total of 77 adolescent patients were recruited from a local public school, of which 23 were without varicocoele and with normal semen analysis (control group), 37 were with varicocoele and normal semen (VNS) parameters, and 17 were with varicocoele and altered semen (VAS) parameters...
May 2016: Andrology
Hideki Katow
Sea urchin mesenchyme is composed of the large micromere-derived spiculogenetic primary mesenchyme cells (PMC), veg2-tier macromere-derived non-spiculogenetic mesenchyme cells, the small micromere-derived germ cells, and the macro- and mesomere-derived neuronal mesenchyme cells. They are formed through the epithelial-to-mesenchymal transition (EMT) and possess multipotency, except PMCs that solely differentiate larval spicules. The process of EMT is associated with modification of epithelial cell surface property that includes loss of affinity to the apical and basal extracellular matrices, inter-epithelial cell adherens junctions and epithelial cell surface-specific proteins...
October 2015: Tissue Barriers
Changgeng Xu, Mingwei Xu, Wei Wang, Jie Zhang
Lefty is a member of the transforming growth factor (TGF) β superfamily, which is implicated in left‑right patterning during embryogenesis. Previous studies revealed that lefty attenuates the epithelial‑mesenchymal transition in tubular epithelial cells. In the present study, the protective effect of lefty1 on renal interstitial injury was further assessed. Mice with a unilateral ureteral obstruction (UUO) were sacrificed on days 3, 5 and 7 following surgery, and the association between the expression of lefty1 and the degree of interstitial fibrosis was investigated...
January 2016: Molecular Medicine Reports
Andre Wendindonde Nana, Pei-Ming Yang, Hung-Yun Lin
Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive of human brain tumors and has a stunning progression with a mean survival of one year from the date of diagnosis. High cell proliferation, angiogenesis and/or necrosis are histopathological features of this cancer, which has no efficient curative therapy. This aggressiveness is associated with particular heterogeneity of the tumor featuring multiple genetic and epigenetic alterations, but also with implications of aberrant signaling driven by growth factors...
2015: Asian Pacific Journal of Cancer Prevention: APJCP
Antonius L van Boxtel, John E Chesebro, Claire Heliot, Marie-Christine Ramel, Richard K Stone, Caroline S Hill
Morphogen signaling is critical for the growth and patterning of tissues in embryos and adults, but how morphogen signaling gradients are generated in tissues remains controversial. The morphogen Nodal was proposed to form a long-range signaling gradient via a reaction-diffusion system, on the basis of differential diffusion rates of Nodal and its antagonist Lefty. Here we use a specific zebrafish Nodal biosensor combined with immunofluorescence for phosphorylated Smad2 to demonstrate that endogenous Nodal is unlikely to diffuse over a long range...
October 26, 2015: Developmental Cell
Jingjing Niu, Conghui Liu, Fang Yang, Zhenwei Wang, Bo Wang, Quanqi Zhang, Yan He, Jie Qi
The nodal signaling pathway has been shown to play crucial roles in inducing and patterning the mesoderm and endoderm, as well as in regulating neurogenesis and left-right axis asymmetry. Here, we present the first complete cDNA and genomic sequences as well as the promoter predication of the Dnah9 gene in the Japanese flounder. The 15,558-bp-long cDNA is divided into 96 exons and spread over 138 kb of genomic DNA. Protein sequence comparison showed that it shares higher identity with other vertebrate orthologs, with an ATP binding dynein motor, AAA domain and microtubule binding stalk of dynein motor...
February 2016: Fish Physiology and Biochemistry
Emmanuel Haillot, Maria Dolores Molina, François Lapraz, Thierry Lepage
Specification of the dorsal-ventral axis in the highly regulative sea urchin embryo critically relies on the zygotic expression of nodal, but whether maternal factors provide the initial spatial cue to orient this axis is not known. Although redox gradients have been proposed to entrain the dorsal-ventral axis by acting upstream of nodal, manipulating the activity of redox gradients only has modest consequences, suggesting that other factors are responsible for orienting nodal expression and defining the dorsal-ventral axis...
2015: PLoS Biology
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