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David K Meyerholz, David A Stoltz, Nick D Gansemer, Sarah E Ernst, Daniel P Cook, Matthew D Strub, Erica N LeClair, Carrie K Barker, Ryan J Adam, Mariah R Leidinger, Katherine N Gibson-Corley, Philip H Karp, Michael J Welsh, Paul B McCray
Loss of cystic fibrosis transmembrane conductance regulator (CFTR) function causes cystic fibrosis (CF), predisposing the lungs to chronic infection and inflammation. In young infants with CF, structural airway defects are increasingly recognized before the onset of significant lung disease, which suggests a developmental origin and a possible role in lung disease pathogenesis. The role(s) of CFTR in lung development is unclear and developmental studies in humans with CF are not feasible. Young CF pigs have structural airway changes and develop spontaneous postnatal lung disease similar to humans; therefore, we studied lung development in the pig model (non-CF and CF)...
February 21, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Qianjin Li, Lishann Ingram, Sungjin Kim, Zanna Beharry, Jonathan A Cooper, Houjian Cai
Cross talk of stromal-epithelial cells plays an essential role in both normal development and tumor initiation and progression. Fibroblast growth factor (FGF)-FGF receptor (FGFR)-Src kinase axis is one of the major signal transduction pathways to mediate this cross talk. Numerous genomic studies have demonstrated that expression levels of FGFR/Src are deregulated in a variety of cancers including prostate cancer; however, the role that paracrine FGF (from stromal cells) plays in dysregulated expression of epithelial FGFRs/Src and tumor progression in vivo is not well evaluated...
February 11, 2018: Neoplasia: An International Journal for Oncology Research
Jiao Li, Zheng Wang, Qiqi Chu, Kewu Jiang, Juan Li, Nan Tang
The differentiation of alveolar epithelial type I (AT1) and type II (AT2) cells is essential for the lung gas exchange function. Disruption of this process results in neonatal death or in severe lung diseases that last into adulthood. We developed live imaging techniques to characterize the mechanisms that control alveolar epithelial cell differentiation. We discovered that mechanical forces generated from the inhalation of amniotic fluid by fetal breathing movements are essential for AT1 cell differentiation...
February 5, 2018: Developmental Cell
Zuzana Dankova, Pavol Zubor, Marian Grendar, Andrea Kapinova, Katarina Zelinova, Mariana Jagelkova, Alexandra Gondova, Karol Dokus, Michal Kalman, Zora Lasabova, Jan Danko
The fibroblast growth factor receptors (FGFRs) and Ras/mitogen activated protein (RAS/MAP) signalling cascades are the main molecular pathways involved in breast carcinogenesis. This study aims to determine the association between FGF10 (rs4415084 C>T), FGFR2 (rs2981582 C>T) and MAP3K1 (rs889312 A>C) gene polymorphisms and breast cancer, to analyse the discriminative ability of each SNP and to test the accuracy of the predictive breast cancer risk model which includes all SNPs. We conducted a case-control study of 170 women (57...
December 2017: General Physiology and Biophysics
Shawn Liang, Ellen Johansson, Guillermo Barila, Daniel L Altschuler, Henrik Fagman, Mikael Nilsson
The developmental program that regulates thyroid progenitor cell proliferation is largely unknown. Here we show that branching-like morphogenesis is a driving force to attain final size of the embryonic thyroid gland in mice. Sox9, a key factor in branching organ development, distinguishes Nkx2-1+ cells in the thyroid bud from progenitors originally forming the thyroid placode in anterior endoderm. As lobes develop the thyroid primordial tissue branches several generations. Sox9 and Fgfr2b are co-expressed distally in the branching epithelium prior to folliculogenesis...
December 22, 2017: Development
Benjamin M Smith, Hussein Traboulsi, John H M Austin, Ani Manichaikul, Eric A Hoffman, Eugene R Bleecker, Wellington V Cardoso, Christopher Cooper, David J Couper, Stephen M Dashnaw, Jia Guo, MeiLan K Han, Nadia N Hansel, Emlyn W Hughes, David R Jacobs, Richard E Kanner, Joel D Kaufman, Eric Kleerup, Ching-Long Lin, Kiang Liu, Christian M Lo Cascio, Fernando J Martinez, Jennifer N Nguyen, Martin R Prince, Stephen Rennard, Stephen S Rich, Leora Simon, Yanping Sun, Karol E Watson, Prescott G Woodruff, Carolyn J Baglole, R Graham Barr
Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette smoking is incompletely understood, although several genetic variants associated with COPD are known to regulate airway branch development. We demonstrate that in vivo central airway branch variants are present in 26.5% of the general population, are unchanged over 10 y, and exhibit strong familial aggregation. The most common airway branch variant is associated with COPD in two cohorts ( n = 5,054), with greater central airway bifurcation density, and with emphysema throughout the lung...
January 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
Li He, Michael R Frost, John T Siegwart, Thomas T Norton
Hyperopic refractive error is detected by retinal neurons, which generate GO signals through a direct emmetropization signaling cascade: retinal pigment epithelium (RPE) into choroid and then into sclera, thereby increasing axial elongation. To examine signaling early in this cascade, we measured gene expression in the retina and RPE after short exposure to hyperopia produced by minus-lens wear. Gene expression in each tissue was compared with gene expression in combined retina + RPE. Starting 24 days after normal eye opening, three groups of juvenile tree shrews (n = 7 each) wore a monocular -5 D lens...
January 9, 2018: Experimental Eye Research
Carina Fischer, Takahiro Seki, Sharon Lim, Masaki Nakamura, Patrik Andersson, Yunlong Yang, Jennifer Honek, Yangang Wang, Yanyan Gao, Fang Chen, Nilesh J Samani, Jun Zhang, Masato Miyake, Seiichi Oyadomari, Akihiro Yasue, Xuri Li, Yun Zhang, Yizhi Liu, Yihai Cao
Understanding the molecular mechanisms regulating beige adipocyte formation may lead to the development of new therapies to combat obesity. Here, we report a miRNA-based autocrine regulatory pathway that controls differentiation of preadipocytes into beige adipocytes. We identify miR-327 as one of the most downregulated miRNAs targeting growth factors in the stromal-vascular fraction (SVF) under conditions that promote white adipose tissue (WAT) browning in mice. Gain- and loss-of-function experiments reveal that miR-327 targets FGF10 to prevent beige adipocyte differentiation...
December 12, 2017: Nature Communications
Eric Lee, Trang Le, Ying Zhu, George Elakis, Anne Turner, William Lo, Hanka Venselaar, Carol-Ann Verrenkamp, Nicole Snow, David Mowat, Edwin Philip Kirk, Rani Sachdev, Janine Smith, Natasha Jane Brown, Mathew Wallis, Chris Barnett, Fiona McKenzie, Mary-Louise Freckmann, Felicity Collins, Maya Chopra, Nerine Gregersen, Ian Hayes, Sulekha Rajagopalan, Tiong Yang Tan, Zornitza Stark, Ravi Savarirayan, Alison Yeung, Lesley Adès, Michael Gattas, Kate Gibson, Michael Gabbett, David John Amor, Wanda Lattanzi, Simeon Boyd, Eric Haan, Mark Gianoutsos, Timothy Chilton Cox, Michael Francis Buckley, Tony Roscioli
PurposeThe craniosynostoses are characterized by premature fusion of one or more cranial sutures. The relative contribution of previously reported genes to craniosynostosis in large cohorts is unclear. Here we report on the use of a massively parallel sequencing panel in individuals with craniosynostosis without a prior molecular diagnosis.MethodsA 20-gene panel was designed based on the genes' association with craniosynostosis, and clinically validated through retrospective testing of an Australian and New Zealand cohort of 233 individuals with craniosynostosis in whom previous testing had not identified a causative variant within FGFR1-3 hot-spot regions or the TWIST1 gene...
December 7, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Julia do Amaral Gomes, Thayne Woycinck Kowalski, Lucas Rosa Fraga, Luciana Tovo-Rodrigues, Maria Teresa Vieira Sanseverino, Lavínia Schuler-Faccini, Fernanda Sales Luiz Vianna
Thalidomide is a drug used worldwide for several indications, but the molecular mechanisms of its teratogenic property are not fully understood. Studies in animal models suggest the oxidative stress, the inhibition of angiogenesis, and the binding to E3-ubiquitin ligase complex as mechanisms by which thalidomide can change the expression of genes important to embryonic development. In this study, seven polymorphisms in genes related to development (FGF8, FGF10, BMP4, SHH, TP53, TP63, and TP73) were analyzed in people with thalidomide embryopathy (TE) and compared to people without malformations...
November 28, 2017: Birth Defects Research
Yujia Yang, Qiang Fu, Yang Liu, Xiaozhu Wang, Rex Dunham, Shikai Liu, Lisui Bao, Qifan Zeng, Tao Zhou, Ning Li, Zhenkui Qin, Chen Jiang, Dongya Gao, Zhanjiang Liu
The swimbladder is an internal gas-filled organ in teleosts. Its major function is to regulate buoyancy. Swimbladder exhibits great variations in size, shape, number of compartments or chambers among teleosts. However, the genomic control of swimbladder variations is unknown. Channel catfish (Ictalurus punctatus), blue catfish (Ictalurus furcatus), and their F1 hybrids of female channel catfish x male blue catfish (C×B hybrid catfish) provide a good model to investigate the swimbladder morphology, because channel catfish possess a single-chambered swimbladder whereas blue catfish possess a bi-chambered swimbladder; and C×B hybrid catfish possess a bi-chambered swimbladder but with significantly reduced posterior chamber...
November 22, 2017: Physiological Genomics
K Nishio, F Tanihara, T-V Nguyen, T Kunihara, M Nii, M Hirata, T Takemoto, T Otoi
This study was conducted to determine suitable conditions for an experimental method in which the CRISPR/Cas9 system is introduced into in vitro-produced porcine zygotes by electroporation. In the first experiment, when putative zygotes derived from in vitro fertilization (IVF) were electroporated by either unipolar or bipolar pulses, keeping the voltage, pulse duration and pulse number fixed at 30 V/mm, 1 msec and five repeats, respectively, the rate of blastocyst formation from zygotes electroporated by bipolar pulses decreased compared to zygotes electroporated by unipolar pulses...
November 14, 2017: Reproduction in Domestic Animals, Zuchthygiene
P Tríbulo, L G B Siqueira, L J Oliveira, T Scheffler, P J Hansen
Knowledge of the molecules used by the maternal reproductive tract to regulate development of the preimplantation embryo is largely incomplete. The goal of the present experiment was to identify candidates for this function. The approach was to assess expression patterns in the endometrium and oviduct of 93 genes encoding for hormones, growth factors, chemokines, cytokines, and WNT-related molecules. Results show that all of the genes were expressed in the reproductive tract. Expression in oviduct was affected by day of the estrous cycle for 21 genes with 11 genes having highest expression at estrus (CCL21, CTGF, CXCL10, CXCL16, DKK3, FGF10, IL18, IL33, IL34, PGF, and SFRP2), one gene at d 3 (WNT4), 8 at d 5 (BMP7, HGF, IL6, SFRP1, TGFB1, WIF1, WNT2, and WNT5A), and one at d 7 (IK)...
November 8, 2017: Journal of Dairy Science
Saunders T Ching, Carlos R Infante, Wen Du, Amnon Sharir, Sungdae Park, Douglas B Menke, Ophir D Klein
Genital malformations are among the most common human birth defects, and both genetic and environmental factors can contribute to these malformations. Development of the external genitalia in mammals relies on complex signaling networks, and disruption of these signaling pathways can lead to genital defects. Islet-1 (ISL1), a member of the LIM/Homeobox family of transcription factors, has been identified as a major susceptibility gene for classic bladder exstrophy in humans, a common form of the bladder exstrophy-epispadias complex (BEEC), and is implicated in a role in urinary tract development...
November 8, 2017: Human Molecular Genetics
Jui-Yen Huang, Marisha Lynn Miskus, Hui-Chen Lu
Fibroblast growth factors (FGFs) and FGF receptors (FGFRs) are known for their potent effects on cell proliferation/differentiation and cortical patterning in the developing brain. However, little is known regarding the roles of FGFs/FGFRs in cortical circuit formation. Here we show that Fgfr1/2/3 and Fgf7/9/10/22 mRNAs are expressed in the developing primary somatosensory (S1) barrel cortex. Barrel cortex layer IV spiny stellate cells (bSCs) are the primary recipients of ascending sensory information via thalamocortical axons (TCAs)...
December 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Maria Jesus Rodrigo, Miriam Idoipe, Silvia Izquierdo, Maria Satue, Antonio Mateo, Antonio Sanchez, Elena Garcia-Martin, Luis Pablo
Aplasia/agenesis of lacrimal and salivary glands is a rare congenital defect that has been associated with disturbances in fibroblast growth factor 10 (FGF10). It can present with symptoms of congenital lacrimal obstruction, dry eye, and dry mouth. We report the ophthalmological and genetic study of a 19-year-old woman and her relatives suffering from this syndrome. A new probably pathogenic variant is described in the FGF10 gene.
January 2018: Ophthalmic Genetics
Ankur Garg, Mukesh Bansal, Noriko Gotoh, Gen-Sheng Feng, Jian Zhong, Fen Wang, Ariana Kariminejad, Steven Brooks, Xin Zhang
The sequential use of signaling pathways is essential for the guidance of pluripotent progenitors into diverse cell fates. Here, we show that Shp2 exclusively mediates FGF but not PDGF signaling in the neural crest to control lacrimal gland development. In addition to preventing p53-independent apoptosis and promoting the migration of Sox10-expressing neural crests, Shp2 is also required for expression of the homeodomain transcription factor Alx4, which directly controls Fgf10 expression in the periocular mesenchyme that is necessary for lacrimal gland induction...
October 2017: PLoS Genetics
Thomas Volckaert, Tingting Yuan, Cho-Ming Chao, Harold Bell, Alina Sitaula, Luisa Szimmtenings, Elie El Agha, Diptiman Chanda, Susan Majka, Saverio Bellusci, Victor J Thannickal, Reinhard Fässler, Stijn P De Langhe
The lung harbors its basal stem/progenitor cells (BSCs) in the protected environment of the cartilaginous airways. After major lung injuries, BSCs are activated and recruited to sites of injury. Here, we show that during homeostasis, BSCs in cartilaginous airways maintain their stem cell state by downregulating the Hippo pathway (resulting in increased nuclear Yap), which generates a localized Fgf10-expressing stromal niche; in contrast, differentiated epithelial cells in non-cartilaginous airways maintain quiescence by activating the Hippo pathway and inhibiting Fgf10 expression in airway smooth muscle cells (ASMCs)...
October 9, 2017: Developmental Cell
Hideki Sugii, Alexandre Grimaldi, Jingyuan Li, Carolina Parada, Thach Vu-Ho, Jifan Feng, Junjun Jing, Yuan Yuan, Yuxing Guo, Hidefumi Maeda, Yang Chai
Craniofacial development depends on cell-cell interactions, coordinated cellular movement and differentiation under the control of regulatory gene networks, which include the distal-less (Dlx) gene family. However, the functional significance of Dlx5 in patterning the oropharyngeal region has remained unknown. Here, we show that loss of Dlx5 leads to a shortened soft palate and an absence of the levator veli palatini, palatopharyngeus and palatoglossus muscles that are derived from the 4th pharyngeal arch (PA); however, the tensor veli palatini, derived from the 1st PA, is unaffected...
November 1, 2017: Development
Jian Chen, Zhouguang Wang, ZengMing Zheng, Yu Chen, Sinan Khor, KeSi Shi, ZiLi He, Qingqing Wang, Yingzheng Zhao, Hongyu Zhang, Xiaokun Li, Jiawei Li, Jiayu Yin, Xiangyang Wang, Jian Xiao
Therapeutics used to treat central nervous system (CNS) injury were designed to repair neurites and inhibit cell apoptosis. Previous studies have shown that neuron-derived FGF10 exerts potential neuroprotective effects after cerebral ischemia injury. However, little is known about the role of endogenous FGF10 in the recovery process after spinal cord injury (SCI). In this study, we found that FGF10 is mainly produced by neuron and microglia/macrophages, and its expression is increased after SCI. Exogenous treatment of FGF10 improved functional recovery after injury by reducing apoptosis, as well as repairing neurites via FGFR2/PI3K/Akt pathway...
October 5, 2017: Cell Death & Disease
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