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https://www.readbyqxmd.com/read/29213092/developmental-nonlinearity-drives-phenotypic-robustness
#1
Rebecca M Green, Jennifer L Fish, Nathan M Young, Francis J Smith, Benjamin Roberts, Katie Dolan, Irene Choi, Courtney L Leach, Paul Gordon, James M Cheverud, Charles C Roseman, Trevor J Williams, Ralph S Marcucio, Benedikt Hallgrímsson
Robustness to perturbation is a fundamental feature of complex organisms. Mutations are the raw material for evolution, yet robustness to their effects is required for species survival. The mechanisms that produce robustness are poorly understood. Nonlinearities are a ubiquitous feature of development that may link variation in development to phenotypic robustness. Here, we manipulate the gene dosage of a signaling molecule, Fgf8, a critical regulator of vertebrate development. We demonstrate that variation in Fgf8 expression has a nonlinear relationship to phenotypic variation, predicting levels of robustness among genotypes...
December 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29193903/genetic-susceptibility-to-thalidomide-embryopathy-in-humans-study-of-candidate-development-genes
#2
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
https://www.readbyqxmd.com/read/29168327/distinct-cerebellar-foliation-anomalies-in-a-chd7-haploinsufficient-mouse-model-of-charge-syndrome
#3
Danielle E Whittaker, Sahrunizam Kasah, Alex P A Donovan, Jacob Ellegood, Kimberley L H Riegman, Holger A Volk, Imelda McGonnell, Jason P Lerch, M Albert Basson
Mutations in the gene encoding the ATP dependent chromatin-remodeling factor, CHD7 are the major cause of CHARGE (Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital-urinary anomalies, and Ear defects) syndrome. Neurodevelopmental defects and a range of neurological signs have been identified in individuals with CHARGE syndrome, including developmental delay, lack of coordination, intellectual disability, and autistic traits. We previously identified cerebellar vermis hypoplasia and abnormal cerebellar foliation in individuals with CHARGE syndrome...
November 23, 2017: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
https://www.readbyqxmd.com/read/29158323/fgf8-morphogen-gradients-are-differentially-regulated-by-heparan-sulphotransferases-hs2st-and-hs6st1-in-the-developing-brain
#4
Wai-Kit Chan, David J Price, Thomas Pratt
Fibroblast growth factor (FGF) morphogen signalling through the evolutionarily ancient Extracellular signaling Regulated Kinase/Mitogen Activated Protein Kinase (ERK/MAPK) pathway recurs in many neural and non-neural developmental contexts and understanding the mechanisms that regulate FGF/ERK function are correspondingly important. The glycosaminoglycan heparan sulphate (HS) binds to FGFs and exists in an enormous number of differentially sulphated forms produced by the action of HS modifying enzymes so has the potential to present an extremely large amount of information in FGF/ERK signalling...
November 20, 2017: Biology Open
https://www.readbyqxmd.com/read/29124740/organizing-activity-of-fgf8-on-the-anterior-telencephalon
#5
Tatsuya Sato, Takako Kikkawa, Tetsuichiro Saito, Keiichi Itoi, Noriko Osumi
The anterior part of the embryonic telencephalon gives rise to several brain regions that are important for animal behavior, including the frontal cortex (FC) and the olfactory bulb. The FC plays an important role in decision-making behaviors, such as social and cognitive behavior, and the olfactory bulb is involved in olfaction. Here, we show the organizing activity of fibroblast growth factor 8 (Fgf8) in the regionalization of the anterior telencephalon, specifically the FC and the olfactory bulb. Misexpression of Fgf8 in the most anterior part of the mouse telencephalon at embryonic day 11...
November 10, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/29068152/review-and-experimental-evaluation-of-the-embryonic-development-and-evolutionary-history-of-flipper-development-and-hyperphalangy-in-dolphins-cetacea-mammalia
#6
Lisa Noelle Cooper, Karen E Sears, Brooke A Armfield, Bhavneet Kala, Merla Hubler, J G M Thewissen
Cetaceans are the only mammals to have evolved hyperphalangy, an increase in the number of phalanges beyond the mammalian plesiomorphic condition of three phalanges per digit. In this study, cetaceans were used as a novel model to review previous studies of mammalian hyperphalangy and contribute new experimental evidence as to the molecular origins of this phenotype in embryos of the pantropical spotted dolphin (Stenella attenuata). Results show embryos of dolphins, mice, and pigs share similar spatiotemporal patterns of signaling proteins known to shape limbs of mammals (e...
October 25, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/29046629/cerebellar-vermis-and-midbrain-hypoplasia-upon-conditional-deletion-of-chd7-from-the-embryonic-mid-hindbrain-region
#7
Alex P A Donovan, Tian Yu, Jacob Ellegood, Kimberley L H Riegman, Christa de Geus, Conny van Ravenswaaij-Arts, Cathy Fernandes, Jason P Lerch, M Albert Basson
Reduced fibroblast growth factor (FGF) signaling from the mid-hindbrain or isthmus organizer (IsO) during early embryonic development results in hypoplasia of the midbrain and cerebellar vermis. We previously reported evidence for reduced Fgf8 expression and FGF signaling in the mid-hindbrain region of embryos heterozygous for Chd7, the gene mutated in CHARGE (Coloboma, Heart defects, choanal Atresia, Retarded growth and development, Genitourinary anomalies and Ear defects) syndrome. However, Chd7(+/-) animals only exhibit mild cerebellar vermis anomalies...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/29042943/suxiao-jiuxin-pill-protects-cardiomyocytes-against-mitochondrial-injury-and-alters-gene-expression-during-ischemic-injury
#8
Xiaofen Ruan, Tiejun Chen, Xiaolong Wang, Yiping Li
Suxiao Jiuxin Pill (SX), a traditional Chinese medicine compound consisting primarily of tetramethylpyrazine and borneol, has been reported to protect against ischemic heart disease. However, the effects of SX on mitochondrial injury and gene expression in various signaling pathways are unclear. The aim of the present study was to investigate the effects of SX on mitochondrial injury and to screen the expression of genes potentially altered by SX using a cell culture model of ischemic injury. Simulated ischemia was established by culturing HL-1 cardiomyocytes in Dulbecco's modified Eagle medium without glucose or serum in a hypoxic chamber containing 95% N2 and 5% CO2 for 24 h...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29029430/methylomics-of-nitroxidative-stress-on-precancerous-cells-reveals-dna-methylation-alteration-at-the-transition-from-in-situ-to-invasive-cervical-cancer
#9
Po-Hsuan Su, Yao-Wen Hsu, Rui-Lan Huang, Yu-Chun Weng, Hui-Chen Wang, Yu-Chih Chen, Yueh-Ju Tsai, Chiou-Chung Yuan, Hung-Cheng Lai
Epigenetic dysregulation is important in cervical cancer development, but the underlying mechanism is largely unknown. Increasing evidence indicates that DNA methylation is sensitive to changes in microenvironmental factors, such as nitric oxide (NO) in the chronic inflammatory cervix. However, the epigenomic effects of NO in cancer have not been investigated. In this study, we explored the methylomic effects of nitroxidative stress in HPV-immortalized precancerous cells. Chronic NO exposure promoted the acquisition of malignant phenotypes such as cell growth, migration, invasion, and anchorage-independent growth...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977614/hypothalamic-%C3%AE-catenin-is-essential-for-fgf8-mediated-anterior-pituitary-growth-links-to-human-disease
#10
Sally A Camper, Alexandre Z Daly, Caitlin E Stallings, Buffy S Ellsworth
No abstract text is available yet for this article.
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28961240/myocardial-wall-stiffening-in-a-mouse-model-of-persistent-truncus-arteriosus
#11
Christine Miller Buffinton, Alyssa K Benjamin, Ashley N Firment, Anne M Moon
BACKGROUND: Genetic and epigenetic programs regulate dramatic structural changes during cardiac morphogenesis. Concurrent biomechanical forces within the heart created by blood flow and pressure in turn drive downstream cellular, molecular and genetic responses. Thus, a genetic-morphogenetic-biomechanical feedback loop is continually operating to regulate heart development. During the evolution of a congenital heart defect, concomitant abnormalities in blood flow, hemodynamics, and patterns of mechanical loading would be predicted to change the output of this feedback loop, impacting not only the ultimate morphology of the defect, but potentially altering tissue-level biomechanical properties of structures that appear structurally normal...
2017: PloS One
https://www.readbyqxmd.com/read/28938441/canonical-wnt-signaling-regulates-the-pituitary-organizer-and-pituitary-gland-formation
#12
Allison M Osmundsen, Jessica L Keisler, M Mark Taketo, Shannon W Davis
The pituitary organizer is a domain within the ventral diencephalon that expresses Bmp4, Fgf8, and Fgf10, which induce the formation of the pituitary precursor, Rathke's pouch, from the oral ectoderm. The WNT signaling pathway regulates this pituitary organizer such that loss of Wnt5a leads to an expansion of the pituitary organizer and an enlargement of Rathke's pouch. WNT signaling is classified into canonical signaling, which is mediated by β-CATENIN, and noncanonical signaling, which operates independently of β-CATENIN...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28898437/regulation-of-fibroblast-growth-factor-8-fgf8-in-chicken-embryonic-stem-cells-differentiation-into-spermatogonial-stem-cells
#13
Man Wang, Chen Zhang, Chuanli Huang, Shaoze Cheng, Nana He, Yilin Wang, Mahmoud F Ahmed, Ruifeng Zhao, Jing Jin, Qisheng Zuo, Yani Zhang, Bichun Li
Fibroblast growth factors (FGFs) are essential in regulating the formation of spermatogonial stem cells (SSCs). Here, we explored the effect of FGF8 on chicken SSCs formation by knockdown or overexpression of FGF8 in chicken embryonic stem cells (ESCs) both in vitro and in vivo. Our results showed that knockdown of FGF8 could facilitate the differentiation of ESCs into SSCs, overexpression of FGF8 could promote PGCs self-renewal, inhibit SSCs formation. This study further revealed the positive correlation between the expression level of FGF8 and MAPK/ERK signal...
September 12, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28892484/six1-is-essential-for-differentiation-and-patterning-of-the-mammalian-auditory-sensory-epithelium
#14
Ting Zhang, Jinshu Xu, Pascal Maire, Pin-Xian Xu
The organ of Corti in the cochlea is a two-cell layered epithelium: one cell layer of mechanosensory hair cells that align into one row of inner and three rows of outer hair cells interdigitated with one cell layer of underlying supporting cells along the entire length of the cochlear spiral. These two types of epithelial cells are derived from common precursors in the four- to five-cell layered primordium and acquire functionally important shapes during terminal differentiation through the thinning process and convergent extension...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28880263/lrp6-is-identified-as-a-potential-prognostic-marker-for-oral-squamous-cell-carcinoma-via-maldi-ims
#15
Yao Yuan, Xiaoyan Xie, Yuchen Jiang, Zihao Wei, Peiqi Wang, Fangman Chen, Xinyi Li, Chongkui Sun, Hang Zhao, Xin Zeng, Lu Jiang, Yu Zhou, Hongxia Dan, Mingye Feng, Rui Liu, Zhiyong Wang, Qianming Chen
Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related deaths worldwide, with 500 000 new cases each year. However, the mechanisms underlying OSCC development are relatively unknown. In this study, matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS)-based proteomic strategy was used to profile the differentially expressed peptides/proteins between OSCC tissues and their adjacent noncancerous tissues. Sixty-seven unique peptide peaks and five distinct proteins were identified with changed expression levels...
September 7, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28870996/vestigial-like-3-is-a-novel-ets1-interacting-partner-and-regulates-trigeminal-nerve-formation-and-cranial-neural-crest-migration
#16
Emilie Simon, Nadine Thézé, Sandrine Fédou, Pierre Thiébaud, Corinne Faucheux
Drosophila Vestigial is the founding member of a protein family containing a highly conserved domain, called Tondu, which mediates their interaction with members of the TEAD family of transcription factors (Scalloped in Drosophila). In Drosophila, the Vestigial/Scalloped complex controls wing development by regulating the expression of target genes through binding to MCAT sequences. In vertebrates, there are four Vestigial-like genes, the functions of which are still not well understood. Here, we describe the regulation and function of vestigial-like 3 (vgll3) during Xenopus early development...
October 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28852180/pathway-based-expression-profiling-of-benign-prostatic-hyperplasia-and-prostate-cancer-delineates-an-immunophilin-molecule-associated-with-cancer-progression
#17
Ankur Bhowal, Subhadipa Majumder, Subarna Ghosh, Sanmitra Basu, Debrup Sen, Susanta Roychowdhury, Sanghamitra Sengupta, Urmi Chatterji
Aberrant restoration of AR activity is linked with prostate tumor growth, therapeutic failures and development of castrate-resistant prostate cancer. Understanding the processes leading to AR-reactivation should provide the foundation for novel avenues of drug discovery. A differential gene expression study was conducted using biopsies from CaP and BPH patients to identify the components putatively responsible for reinstating AR activity in CaP. From the set of genes upregulated in CaP, FKBP52, an AR co-chaperone, was selected for further analysis...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28843494/phosphorylation-of-lbx1-controls-lateral-myoblast-migration-into-the-limb
#18
COMPARATIVE STUDY
Wouter Masselink, Megumi Masaki, Daniel Sieiro, Christophe Marcelle, Peter D Currie
The migration of limb myogenic precursors from limb level somites to their ultimate site of differentiation in the limb is a paradigmatic example of a set of dynamic and orchestrated migratory cell behaviours. The homeobox containing transcription factor ladybird homeobox 1 (Lbx1) is a central regulator of limb myoblast migration, null mutations of Lbx1 result in severe disruptions to limb muscle formation, particularly in the distal region of the limb in mice (Gross et al., 2000). As such Lbx1 has been hypothesized to control lateral migration of myoblasts into the distal limb anlage...
October 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28791365/fgf8-promotes-cell-proliferation-and-resistance-to-egfr-inhibitors-via-upregulation-of-egfr-in-human-hepatocellular-carcinoma-cells
#19
Yuanmin Pei, Xueling Sun, Xiwei Guo, Huashan Yin, Le Wang, Fugu Tian, Hongxi Jing, Xiaobo Liang, Jun Xu, Pengcheng Shi
Fibroblast growth factor 8 (FGF8), a member of the fibroblast growth factor (FGF) family, is upregulated in several human cancers, including HCC (HCC). Previous studies have demonstrated that FGF8 increased cell growth and invasion of tumor cells. In the present study we investigated whether FGF8 is involved in the cell proliferation and resistance to several drugs in human HCC cells. We stably overexpressed FGF8 by lentiviral transfection. In addition, we also added recombinant FGF8 instead of stably overexpressing FGF8 in human HCC cells...
August 7, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28754980/regulation-of-sema3c-and-the-interaction-between-cardiac-neural-crest-and-second-heart-field-during-outflow-tract-development
#20
Kazuki Kodo, Shinsuke Shibata, Sachiko Miyagawa-Tomita, Sang-Ging Ong, Hiroshi Takahashi, Tsutomu Kume, Hideyuki Okano, Rumiko Matsuoka, Hiroyuki Yamagishi
The cardiac neural crest cells (cNCCs) and the second heart field (SHF) play key roles in development of the cardiac outflow tract (OFT) for establishment of completely separated pulmonary and systemic circulations in vertebrates. A neurovascular guiding factor, Semaphorin 3c (Sema3c), is required for the development of the OFT, however, its regulation of the interaction between cNCCs and SHF remains to be determined. Here, we show that a Sema3c is a candidate that mediates interaction between cNCCs and the SHF during development of the OFT...
July 28, 2017: Scientific Reports
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