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Marta Mikolajczak, Timothy Goodman, Mohammad K Hajihosseini
Heterozygous mutations in the gene encoding fibroblast growth factor 10 (FGF10) or its cognate receptor, FGF-receptor 2 IIIb (FGFR2-IIIb) result in two human syndromes - LADD (lacrimo-auriculo-dento-digital) and ALSG (Aplasia of lacrimal and salivary glands). To date, the partial loss-of-FGF10 function in these patients has been attributed solely to perturbed paracrine signalling functions between FGF10-producing mesenchymal cells and FGF10-responsive epithelial cells. However, the functioning of a LADD-causing G138E FGF10 mutation, which falls outside its receptor interaction interface, has remained enigmatic...
October 14, 2016: Biochemical Journal
L C Wu, C Liu, M R Jiang, Y M Jiang, Q H Wang, Z Y Lu, S J Wang, W L Yang, Y X Shao
Development of the eyelid requires coordination of the cellular processes involved in proliferation, cell size alteration, migration, and cell death. C57BL/6J-corneal opacity (B6-Co) mice are mutant mice generated by the administration of N-ethyl-N-nitrosourea (100 mg/kg). They exhibit the eyelids open at birth phenotype, abnormal round cell shape from tightened F-actin bundles in leading edge keratinocytes at E16.5, and gradual corneal opacity with neovessels. The tip of the leading edge in B6-Co mice did not move forward, and demonstrated a sharp peak shape without obvious directionality...
August 26, 2016: Genetics and Molecular Research: GMR
Elizabeth P Bless, Jane Yang, Kalpana D Acharya, Sabin A Nettles, Fair M Vassoler, Elizabeth M Byrnes, Marc J Tetel
Estrogens and leptins act in the hypothalamus to maintain reproduction and energy homeostasis. Neurogenesis in the adult mammalian hypothalamus has been implicated in the regulation of energy homeostasis. Recently, high-fat diet (HFD) and estradiol (E2) have been shown to alter cell proliferation and the number of newborn leptin-responsive neurons in the hypothalamus of adult female mice. The current study tested the hypothesis that new cells expressing estrogen receptor α (ERα) are generated in the arcuate nucleus (ARC) and the ventromedial nucleus of the hypothalamus (VMH) of the adult female mouse, hypothalamic regions that are critical in energy homeostasis...
July 2016: ENeuro
Maya Ghoussaini, Juliet D French, Kyriaki Michailidou, Silje Nord, Jonathan Beesley, Sander Canisus, Kristine M Hillman, Susanne Kaufmann, Haran Sivakumaran, Mahdi Moradi Marjaneh, Jason S Lee, Joe Dennis, Manjeet K Bolla, Qin Wang, Ed Dicks, Roger L Milne, John L Hopper, Melissa C Southey, Marjanka K Schmidt, Annegien Broeks, Kenneth Muir, Artitaya Lophatananon, Peter A Fasching, Matthias W Beckmann, Olivia Fletcher, Nichola Johnson, Elinor J Sawyer, Ian Tomlinson, Barbara Burwinkel, Frederik Marme, Pascal Guénel, Thérèse Truong, Stig E Bojesen, Henrik Flyger, Javier Benitez, Anna González-Neira, M Rosario Alonso, Guillermo Pita, Susan L Neuhausen, Hoda Anton-Culver, Hermann Brenner, Volker Arndt, Alfons Meindl, Rita K Schmutzler, Hiltrud Brauch, Ute Hamann, Daniel C Tessier, Daniel Vincent, Heli Nevanlinna, Sofia Khan, Keitaro Matsuo, Hidemi Ito, Thilo Dörk, Natalia V Bogdanova, Annika Lindblom, Sara Margolin, Arto Mannermaa, Veli-Matti Kosma, Anna H Wu, David Van Den Berg, Diether Lambrechts, Giuseppe Floris, Jenny Chang-Claude, Anja Rudolph, Paolo Radice, Monica Barile, Fergus J Couch, Emily Hallberg, Graham G Giles, Christopher A Haiman, Loic Le Marchand, Mark S Goldberg, Soo H Teo, Cheng Har Yip, Anne-Lise Borresen-Dale, Wei Zheng, Qiuyin Cai, Robert Winqvist, Katri Pylkäs, Irene L Andrulis, Peter Devilee, Rob A E M Tollenaar, Montserrat García-Closas, Jonine Figueroa, Per Hall, Kamila Czene, Judith S Brand, Hatef Darabi, Mikael Eriksson, Maartje J Hooning, Linetta B Koppert, Jingmei Li, Xiao-Ou Shu, Ying Zheng, Angela Cox, Simon S Cross, Mitul Shah, Valerie Rhenius, Ji-Yeob Choi, Daehee Kang, Mikael Hartman, Kee Seng Chia, Maria Kabisch, Diana Torres, Craig Luccarini, Don M Conroy, Anna Jakubowska, Jan Lubinski, Suleeporn Sangrajrang, Paul Brennan, Curtis Olswold, Susan Slager, Chen-Yang Shen, Ming-Feng Hou, Anthony Swerdlow, Minouk J Schoemaker, Jacques Simard, Paul D P Pharoah, Vessela Kristensen, Georgia Chenevix-Trench, Douglas F Easton, Alison M Dunning, Stacey L Edwards
Genome-wide association studies (GWASs) have revealed increased breast cancer risk associated with multiple genetic variants at 5p12. Here, we report the fine mapping of this locus using data from 104,660 subjects from 50 case-control studies in the Breast Cancer Association Consortium (BCAC). With data for 3,365 genotyped and imputed SNPs across a 1 Mb region (positions 44,394,495-45,364,167; NCBI build 37), we found evidence for at least three independent signals: the strongest signal, consisting of a single SNP rs10941679, was associated with risk of estrogen-receptor-positive (ER(+)) breast cancer (per-g allele OR ER(+) = 1...
October 6, 2016: American Journal of Human Genetics
Akiko Takikawa, Arshad Mahmood, Allah Nawaz, Tomonobu Kado, Keisuke Okabe, Seiji Yamamoto, Aminuddin Arif, Satoko Senda, Koichi Tsuneyama, Masashi Ikutani, Yasuharu Watanabe, Yoshiko Igarashi, Yoshinori Nagai, Kiyoshi Takatsu, Keiichi Koizumi, Johji Imura, Nobuhito Goda, Masakiyo Sasahara, Michihiro Matsumoto, Kumiko Saeki, Takashi Nakagawa, Shiho Fujisaka, Isao Usui, Kazuyuki Tobe
Adipose tissue hypoxia is an important feature of pathological adipose tissue expansion. Hypoxia-inducible factor-1α (HIF-1α) in adipocytes reportedly induces oxidative stress and fibrosis, rather than neoangiogenesis via VEGF-A. We previously reported that macrophages in crown-like structures (CLSs) are both hypoxic and inflammatory. In the present study, we examined how macrophage HIF-1α is involved in high-fat diet (HFD)-induced inflammation, neovascularization, hypoxia, and insulin resistance using mice with myeloid cell-specific HIF-1α deletion fed an HFD...
September 13, 2016: Diabetes
Alison May, Denis Headon, David Rice, Alistair Noble, Abigail S Tucker
Hypertrophy, hyperplasia and altered mucus secretion from the respiratory submucosal glands (SMG) are characteristics of airway diseases such as cystic fibrosis, asthma and chronic bronchitis. More commonly, hyper-secretion of the nasal SMGs contributes to allergic rhinitis and upper airway infection. Considering the role of these glands in disease states, there is a significant dearth in understanding the molecular signals that regulate SMG development and patterning. Due to the imperative role of FGF signalling during the development of other branched structures, we investigated the role of Fgf10 during initiation and branching morphogenesis of murine nasal SMGs...
August 30, 2016: Developmental Biology
Yong Huan Song, Yu Ting Zhu, Jian Ding, Fei Ya Zhou, Ji Xin Xue, Jin Hee Jung, Zhi Jie Li, Wei Yang Gao
Fibroblast growth factor (FGF)2/basic FGF is a member of the fibroblast growth factor family. Its function in skin wound healing has been well-characterized. However, the function of other FGFs in skin tissues remains to be elucidated. In the present study, FGF expression patterns in heart, liver, skin and kidney tissues were analyzed. Notably, in contrast to other tissues, only four FGFs, FGF2, 7, 10 and 21, were dominant in the skin. To examine FGF function in the wound healing process, mouse NIH3T3 fibroblast cells were treated with FGF2, FGF10 and FGF21, and cell migration was monitored...
October 2016: Molecular Medicine Reports
Xing Chen, Xiao-Ming Hou, You-Fei Fan, Yu-Ting Jin, Yu-Lin Wang
The sonic hedgehog (SHH) morphogen regulates cell differentiation and controls a number of genes during renal morphogenesis. To date, the effects of SHH on fibroblast growth factors (Fgfs) in embryonic kidney development remain unclear. In the present study, explants of BALB/c mouse embryonic kidney tissues were used to investigate the role of exogenous SHH on Fgf8 and Fgf10 expression levels ex vivo. Ureteric bud branches and epithelial metanephric derivatives were used to determine the renal morphogenesis with Dolichos biflorus agglutinin or hematoxylin‑eosin staining...
October 2016: Molecular Medicine Reports
Norifumi Tatsumi, Ritsuko Kobayashi, Tohru Yano, Masatsugu Noda, Koji Fujimura, Norihiro Okada, Masataka Okabe
The lung is an important organ for air breathing in tetrapods and originated well before the terrestrialization of vertebrates. Therefore, to better understand lung evolution, we investigated lung development in the extant basal actinopterygian fish Senegal bichir (Polypterus senegalus). First, we histologically confirmed that lung development in this species is very similar to that of tetrapods. We also found that the mesenchymal expression patterns of three genes that are known to play important roles in early lung development in tetrapods (Fgf10, Tbx4, and Tbx5) were quite similar to those of tetrapods...
2016: Scientific Reports
Ioannis Kyrou, Martin O Weickert, Seley Gharanei, Harpal S Randeva, Bee K Tan
The fibroblast growth factor (FGF) family consists of 22 evolutionarily and structurally related proteins (FGF1 to FGF23; with FGF15 being the rodent ortholog of human FGF19). Based on their mechanism of action, FGFs can be categorized into intracrine, autocrine/paracrine and endocrine subgroups. Both autocrine/paracrine and endocrine FGFs are secreted from their cells of origin and exert their effects on target cells by binding to and activating specific single-pass transmembrane tyrosine kinase receptors (FGFRs)...
July 14, 2016: Minerva Endocrinologica
Nicole B Burger, Monique C Haak, Evelien Kok, Christianne J M de Groot, Weinian Shou, Peter J Scambler, Youngsook Lee, Eunjin Cho, Vincent M Christoffels, Mireille N Bekker
BACKGROUND: In human fetuses with cardiac defects and increased nuchal translucency, abnormal ductus venosus flow velocity waveforms are observed. It is unknown whether abnormal ductus venosus flow velocity waveforms in fetuses with increased nuchal translucency are a reflection of altered cardiac function or are caused by local morphological alterations in the ductus venosus. AIM: The aim of this study was to investigate if the observed increased nuchal translucency, cardiac defects and abnormal lymphatic development in the examined mouse models are associated with local changes in ductus venosus morphology...
October 2016: Early Human Development
Erika Yeh, Rodrigo Atique, Roberto Dalto Fanganiello, Daniele Yumi Sunaga, Felipe Augusto André Ishiy, Maria Rita Passos-Bueno
Apert Syndrome (AS) is one of the most severe forms of craniosynostosis. It is caused by gain-of-function mutations in the receptor fibroblast growth factor receptor 2 (FGFR2), which leads to ligand-receptor promiscuity. Here, we aimed to better understand the behavior of mesenchymal stem cells (MSCs) and of fibroblastoid cells, cellular populations that are part of the suture complex, when stimulated with different fibroblast growth factors (FGFs). We also aimed to verify whether FGFR2 specificity loss due to AS mutations would change their signaling behavior...
August 15, 2016: Stem Cells and Development
Jennifer Quantius, Carole Schmoldt, Ana I Vazquez-Armendariz, Christin Becker, Elie El Agha, Jochen Wilhelm, Rory E Morty, István Vadász, Konstantin Mayer, Stefan Gattenloehner, Ludger Fink, Mikhail Matrosovich, Xiaokun Li, Werner Seeger, Juergen Lohmeyer, Saverio Bellusci, Susanne Herold
Influenza Virus (IV) pneumonia is associated with severe damage of the lung epithelium and respiratory failure. Apart from efficient host defense, structural repair of the injured epithelium is crucial for survival of severe pneumonia. The molecular mechanisms underlying stem/progenitor cell mediated regenerative responses are not well characterized. In particular, the impact of IV infection on lung stem cells and their regenerative responses remains elusive. Our study demonstrates that a highly pathogenic IV infects various cell populations in the murine lung, but displays a strong tropism to an epithelial cell subset with high proliferative capacity, defined by the signature EpCamhighCD24lowintegrin(α6)high...
June 2016: PLoS Pathogens
Minami Shibuya, Tatsuya Ikari, Goro Sugiyama, Yukiko Ohyama, Wataru Kumamaru, Koki Nagano, Tsuyoshi Sugiura, Kanemitsu Shirasuna, Yoshihide Mori
Salivary gland (SG) defects have a wide range of health implications, including xerostomia, bacterial infections, and oral health issues. Branching morphogenesis is critical for SG development. A clear understanding of the mechanisms underlying this process will accelerate SG regeneration studies. Fibroblast growth factor receptor 2 (FGFR2) interacts with multiple fibroblast growth factors (FGFs), which promote development. FGFR2 consists of two isoforms, FGFR2b and FGFR2c. FGFR2b is critical for SG development, but little is known about the expression and function of FGFR2c...
May 17, 2016: Differentiation; Research in Biological Diversity
Chih-Kuan Chen, Chen Siang Ng, Siao-Man Wu, Jiun-Jie Chen, Po-Liang Cheng, Ping Wu, Mei-Yeh Jade Lu, Di-Rong Chen, Cheng-Ming Chuong, Hsu-Chen Cheng, Chau-Ti Ting, Wen-Hsiung Li
Birds can be classified into altricial and precocial. The hatchlings of altricial birds are almost naked, whereas those of precocial birds are covered with natal down. This regulatory divergence is thought to reflect environmental adaptation, but the molecular basis of the divergence is unclear. To address this issue, we chose the altricial zebra finch and the precocial chicken as the model animals. We noted that zebra finch hatchlings show natal down growth suppressed anterior dorsal (AD) skin but partially down-covered posterior dorsal (PD) skin...
August 2016: Molecular Biology and Evolution
Bruno D A Sanches, Juliana S Maldarine, Bruno C Zani, Manoel F Biancardi, Fernanda C A Santos, Rejane M Góes, Patricia S L Vilamaior, Sebastião R Taboga
The development of the prostate gland in females has not yet been clearly elucidated, and the sexual dimorphism associated with such gland development in general is far from being understood. In the present study, we used tridimensional (3D) reconstructions and histochemical and immunohistochemical techniques to describe the sexual dimorphism and its causes in the early postnatal development of the prostate in male and female Mongolian gerbils (Meriones unguiculatus). We observed that the female prostate was smaller, had fewer branches throughout the development, and underwent differentiation earlier than that in males...
August 2016: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
Maxwell C K Leung, M Shane Hutson, Ashley W Seifert, Richard M Spencer, Thomas B Knudsen
Hypospadias is a developmental defect of urethral tube closure that has a complex etiology involving genetic and environmental factors, including anti-androgenic and estrogenic disrupting chemicals; however, little is known about the morphoregulatory consequences of androgen/estrogen balance during genital tubercle (GT) development. Computer models that predictively model sexual dimorphism of the GT may provide a useful resource to translate chemical-target bipartite networks and their developmental consequences across the human-relevant chemical universe...
September 2016: Reproductive Toxicology
Jumpei Terakawa, Altea Rocchi, Vanida A Serna, Erwin P Bottinger, Jonathan M Graff, Takeshi Kurita
Cell fate of lower Müllerian duct epithelium (MDE), to become uterine or vaginal epithelium, is determined by the absence or presence of ΔNp63 expression, respectively. Previously, we showed that SMAD4 and runt-related transcription factor 1 (RUNX1) were independently required for MDE to express ΔNp63. Here, we report that vaginal mesenchyme directs vaginal epithelial cell fate in MDE through paracrine activation of fibroblast growth factor (FGF) receptor-MAPK pathway. In the developing reproductive tract, FGF7 and FGF10 were enriched in vaginal mesenchyme, whereas FGF receptor 2IIIb was expressed in epithelia of both the uterus and vagina...
July 2016: Molecular Endocrinology
Nobuyuki Itoh, Yoshiaki Nakayama, Morichika Konishi
The liver plays important roles in multiple processes including metabolism, the immune system, and detoxification and also has a unique capacity for regeneration. FGFs are growth factors that have diverse functions in development, health, and disease. The FGF family now comprises 22 members. Several FGFs have been shown to play roles as paracrine signals in liver development, health, and disease. FGF8 and FGF10 are involved in embryonic liver development, FGF7 and FGF9 in repair in response to liver injury, and FGF5, FGF8, FGF9, FGF17, and FGF18 in the development and progression of hepatocellular carcinoma...
2016: Frontiers in Cell and Developmental Biology
Lorenzo Alibardi
Previous studies have shown that Fibroblast Growth Factors are present in the regenerating tail tissues of lizards where they may stimulate the process of regeneration. The present study is focused on the immunolocalization of FGF8 and FGF10 in the regenerating lizard tail, two signaling proteins of the apical epidermal cup/ridge and mesenchymal blastema sustaining tail and limb regeneration in amphibians and the development of the tail and limbs in vertebrate embryos. Main immunoreactive protein bands at 15-18kDa for FGF8/10 are detected in the regenerating epidermis and only a band at 30 or 35kDa in the underlying connective tissues...
July 2016: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
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