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Kenneth M McCullough, Dennis Choi, Jidong Guo, Kelsey Zimmerman, Jordan Walton, Donald G Rainnie, Kerry J Ressler
Molecular characterization of neuron populations, particularly those controlling threat responses, is essential for understanding the cellular basis of behaviour and identifying pharmacological agents acting selectively on fear-controlling circuitry. Here we demonstrate a comprehensive workflow for identification of pharmacologically tractable markers of behaviourally characterized cell populations. Thy1-eNpHR-, Thy1-Cre- and Thy1-eYFP-labelled neurons of the BLA consistently act as fear inhibiting or 'Fear-Off' neurons during behaviour...
October 21, 2016: Nature Communications
Minoru Yuriguchi, Hitomi Aoki, Nobuhiko Taguchi, Takahiro Kunisada
BACKGROUND: After severe wounding, hair follicles were known to be regenerated de novo along with the re-epithelialization. However, the regenerated hairs lack pigmentation. OBJECTIVE: We aimed to find out the condition to regenerate pigmented hairs after severe wounding. METHODS: De novo hair regeneration was observed during the re-epithelialization process after the full thickness excision of dorsal skin. Hair pigmentation mechanism was assessed by the modulation of Wnt and Kit signalings...
October 2016: Journal of Dermatological Science
Adeline Jacquinet, Debra Millar, Anna Lehman
Ranging from aplastic uterus (including Mayer-Rokitansky-Kuster-Hauser syndrome) to incomplete septate uterus, uterine malformations as a group are relatively frequent in the general population. Specific causes remain largely unknown. Although most occurrences ostensibly seem sporadic, familial recurrences have been observed, which strongly implicate genetic factors. Through the study of animal models, human syndromes, and structural chromosomal variation, several candidate genes have been proposed and subsequently tested with targeted methods in series of individuals with isolated, non-isolated, or syndromic uterine malformations...
August 2016: American Journal of Medical Genetics. Part A
Luca Muzio, Valentina Brambilla, Lorenza Calcaterra, Patrizia D'Adamo, Gianvito Martino, Francesco Benedetti
The search for biomarkers of antidepressant effects focused on pathways regulating synaptic plasticity, and on activated inflammatory markers. Repeated Sleep Deprivation (SD) provides a model treatment to reverse-translate antidepressant effects from in vivo clinical psychiatry to model organisms. We studied the effects of repeated SD alone (ASD) or combined with exercise on a slow spinning wheel (SSW), in 116 C57BL/6J male mice divided in three groups (ASD, SSW, untreated). Forced Swimming Test (FST) was used to detect antidepressant-like effects...
September 15, 2016: Behavioural Brain Research
James A MacLean, Mandy L King, Hiroshi Okuda, Kanako Hayashi
WNT signaling is well known to play an important role in the regulation of development, cell proliferation and cell differentiation in a wide variety of normal and cancerous tissues. Despite the wealth of knowledge concerning when and where various WNT genes are expressed and downstream events under their control, there is surprisingly little published evidence of how they are regulated. We have recently reported that aberrant WNT7A is observed in serous ovarian carcinomas, and WNT7A is the sole ligand accelerating ovarian tumor progression through CTNNB1 (β-catenin)/TCF signaling in the absence of CTNNB1 mutations...
2016: PloS One
Yuanyuan Li, Xin Tian, Ming Ma, Stephanie Jerman, Shanshan Kong, Stefan Somlo, Zhaoxia Sun
The gene for ADP ribosylation factor-like GTPase 13B (Arl13b) encodes a small GTPase essential for cilia biogenesis in multiple model organisms. Inactivation of arl13b in zebrafish leads to a number of phenotypes indicative of defective cilia, including cystic kidneys. In mouse, null mutation in Arl13b results in severe patterning defects in the neural tube and defective Hedgehog signaling. Human mutations of ARL13B lead to Joubert syndrome, a ciliopathy. However, patients with mutated ARL13B do not develop kidney cysts...
December 2016: Journal of the American Society of Nephrology: JASN
A Al Naib, H L M Tucker, G Xie, D H Keisler, F F Bartol, R P Rhoads, R M Akers, M L Rhoads
Prepubertal exposure of the developing ovaries and reproductive tract (RT) to estrogen or xenoestrogens can have acute and long-term consequences that compromise the reproductive performance of cattle. This research examined effects of the selective estrogen receptor modulator tamoxifen (TAM) on gene and protein abundance in prepubertal ovaries and RT, with a particular focus on signaling pathways that affect morphology. Tamoxifen was administered to Holstein heifer calves (n=8) daily (0.3mg/kg subcutaneously) from 28 to 120 d of age, when tissues were collected...
July 2016: Journal of Dairy Science
Makoto Noda, Mario Vallon, Calvin J Kuo
The transformation suppressor gene RECK was isolated by cDNA expression cloning (1998), and GPR124/TEM5 was detected as a tumor endothelial marker by differential screening (2000). The importance of Wnt7a/b and Gpr124 in brain angiogenesis was demonstrated by reverse genetics in mice (2008-2010). A series of recent studies using genetically engineered mice and zebrafish as well as luciferase reporter assays in cultured cells led to the discovery of functional interactions among Reck, Gpr124, and Wnt7a/b in triggering canonical Wnt signaling with relevance to embryonic brain angiogenesis and blood-brain barrier formation...
May 2016: Cancer Science
Paola I Ingaramo, María M Milesi, Marlise Guerrero Schimpf, Jorge G Ramos, Lucía Vigezzi, Mónica Muñoz-de-Toro, Enrique H Luque, Jorgelina Varayoud
Neonatal exposure to a low dose of endosulfan may disrupt the expression of Wnt7a and β-catenin during uterine development leading to the failure of uterine functional differentiation during implantation. New-born female Wistar rats were treated with vehicle, endosulfan (600 μg/kg/d, E600) or diethylstilbestrol (0.2 μg/kg/d, DES) on postnatal days (PNDs) 1, 3, 5 and 7. Subsequently, uterine histomorphology and the protein expression of Wnt7a and β-catenin were evaluated on PND8, PND21 and gestational day (GD) 5 (pre-implantation period)...
April 15, 2016: Molecular and Cellular Endocrinology
Lucía Vigezzi, Jorge G Ramos, Laura Kass, María V Tschopp, Mónica Muñoz-de-Toro, Enrique H Luque, Verónica L Bosquiazzo
Here we assessed the effects of perinatal exposure to bisphenol A (BPA) on the uterine response to 17β-estradiol (E2) in aged rats. Pregnant rats were orally exposed to 0.5 or 50 μg BPA/kg/day from gestational day 9 until weaning. On postnatal day (PND) 360, the rats were ovariectomized and treated with E2 for three months. The uterine tissue of BPA50 and BPA0.5 rats showed increased density of glands with squamous metaplasia (GSM) and glands with daughter glands respectively. Wnt7a expression was lower in GSM of BPA50 rats than in controls...
May 5, 2016: Molecular and Cellular Endocrinology
Lydia Ferguson, Elena M Kaftanovskaya, Carmen Manresa, Agustin M Barbara, Robert J Poppiti, Yingchun Tan, Alexander I Agoulnik
The Notch signaling pathway is critical for the differentiation of many tissues and organs in the embryo. To study the consequences of Notch1 gain-of-function signaling on female reproductive tract development, we used a cre-loxP strategy and Amhr2-cre transgene to generate mice with conditionally activated Notch1 (Rosa(Notch1)). The Amhr2-cre transgene is expressed in the mesenchyme of developing female reproductive tract and in granulosa cells in the ovary. Double transgenic Amhr2-cre, Rosa(Notch1) females were infertile, whereas control Rosa(Notch1) mice had normal fertility...
March 2016: Biology of Reproduction
K Long, L Moss, L Laursen, L Boulter, C ffrench-Constant
Development of the cerebral cortex requires regulation of proliferation and differentiation of neural stem cells and a diverse range of progenitors. Recent work suggests a role for extracellular matrix (ECM) and the major family of ECM receptors, the integrins. Here we show that enhancing integrin beta-1 signalling, by expressing a constitutively active integrin beta-1 (CA*β1) in the embryonic chick mesencephalon, enhances neurogenesis and increases the number of mitotic cells dividing away from the ventricular surface, analogous to sub-apical progenitors in mouse...
2016: Nature Communications
Alexandra Avgustinova, Marjan Iravani, David Robertson, Antony Fearns, Qiong Gao, Pamela Klingbeil, Andrew M Hanby, Valerie Speirs, Erik Sahai, Fernando Calvo, Clare M Isacke
Stromal fibroblast recruitment to tumours and activation to a cancer-associated fibroblast (CAF) phenotype has been implicated in promoting primary tumour growth and progression to metastatic disease. However, the mechanisms underlying the tumour:fibroblast crosstalk that drive the intertumoural stromal heterogeneity remain poorly understood. Using in vivo models we identify Wnt7a as a key factor secreted exclusively by aggressive breast tumour cells, which induces CAF conversion. Functionally, this results in extracellular matrix remodelling to create a permissive environment for tumour cell invasion and promotion of distant metastasis...
2016: Nature Communications
Tychele N Turner, Fereydoun Hormozdiari, Michael H Duyzend, Sarah A McClymont, Paul W Hook, Ivan Iossifov, Archana Raja, Carl Baker, Kendra Hoekzema, Holly A Stessman, Michael C Zody, Bradley J Nelson, John Huddleston, Richard Sandstrom, Joshua D Smith, David Hanna, James M Swanson, Elaine M Faustman, Michael J Bamshad, John Stamatoyannopoulos, Deborah A Nickerson, Andrew S McCallion, Robert Darnell, Evan E Eichler
We performed whole-genome sequencing (WGS) of 208 genomes from 53 families affected by simplex autism. For the majority of these families, no copy-number variant (CNV) or candidate de novo gene-disruptive single-nucleotide variant (SNV) had been detected by microarray or whole-exome sequencing (WES). We integrated multiple CNV and SNV analyses and extensive experimental validation to identify additional candidate mutations in eight families. We report that compared to control individuals, probands showed a significant (p = 0...
January 7, 2016: American Journal of Human Genetics
Renata Prunskaite-Hyyryläinen, Ilya Skovorodkin, Qi Xu, Ilkka Miinalainen, Jingdong Shan, Seppo J Vainio
The Müllerian duct (MD) is the anlage of the oviduct, uterus and upper part of the vagina, the main parts of the female reproductive tract. Several wingless-type mouse mammary tumor virus (MMTV) integration site family member (Wnt) genes, including Wnt4, Wnt5a and Wnt7a, are involved in the development of MD and its derivatives, with Wnt4 particularly critical, since the MD fails to develop in its absence. We use, here, Wnt4(EGFPCre)-based fate mapping to demonstrate that the MD tip cells and the subsequent MD cells are derived from Wnt4+ lineage cells...
March 15, 2016: Human Molecular Genetics
Hyun Jung Kwak, Dong Won Park, Ji-Young Seo, Ji-Yong Moon, Tae Hyung Kim, Jang Won Sohn, Dong Ho Shin, Ho Joo Yoon, Sung Soo Park, Sang-Heon Kim
Airway remodeling is a key characteristic of chronic asthma, particularly in patients with a fixed airflow limitation. The mechanisms underlying airway remodeling are poorly understood, and no therapeutic option is available. The Wnt/β-catenin signaling pathway is involved in various physiological and pathological processes, including fibrosis and smooth muscle hypertrophy. In this study, we investigated the roles of Wnt/β-catenin signaling in airway remodeling in patients with asthma. Wnt7a mRNA expression was prominent in induced sputum from patients with asthma compared with that from healthy controls...
2015: Experimental & Molecular Medicine
Joseph C Chen, Jacquelyn R Hoffman, Ripla Arora, Lila A Perrone, Christian J Gonzalez-Gomez, Kim Chi Vo, Diana J Laird, Juan C Irwin, Linda C Giudice
OBJECTIVE: To develop a protocol for cryopreservation and recovery of human endometrial epithelial cells (eECs) retaining molecular and functional characteristics of endometrial epithelium in vivo. DESIGN: In vitro study using human endometrial cells. SETTING: University research laboratory. PATIENT(S): Endometrial biopsies were obtained from premenopausal women undergoing benign gynecologic procedures. INTERVENTION(S): Primary eECs were cryopreserved in 1% fetal bovine serum/10% dimethylsulfoxide in Defined Keratinocyte Serum-Free Medium (KSFM)...
February 2016: Fertility and Sterility
R K Bikkavilli, S Avasarala, M Van Scoyk, J Arcaroli, C Brzezinski, W Zhang, M G Edwards, M K K Rathinam, T Zhou, J Tauler, S Borowicz, Y A Lussier, B A Parr, C D Cool, R A Winn
No abstract text is available yet for this article.
October 16, 2015: Oncogene
A V Kuznetsova, A M Kurinov, E V Chentsova, P V Makarov, M A Aleksandrova
Human recombinant protein Wnt7a (hrWnt7a) inhibits cell proliferative activity and triggers cell polarization. Although cell polarization process was maintained only over a short time, probably via microenvironmental stimuli, hrWnt7a is involved in the transformation of the retinal pigment epithelium. Analysis of Wnt signaling pathway and its regulation will help to understand the processes in retinal pigment epithelial cells under pathological conditions, which can be useful in developing new generation drugs...
August 2015: Bulletin of Experimental Biology and Medicine
Imran Nawaz, Li-Fu Hu, Zi-Ming Du, Khalid Moumad, Ilya Ignatyev, Tatiana V Pavlova, Vladimir Kashuba, Malin Almgren, Eugene R Zabarovsky, Ingemar Ernberg
Epigenetic silencing of tumor suppressor genes (TSGs) by promoter methylation can be an early event in the multi-step process of carcinogenesis. Human chromosome 3 contains clusters of TSGs involved in many cancer types including nasopharyngeal carcinoma (NPC), the most common cancer in Southern China. Among ten candidate TSGs identified in chromosome 3 using NotI microarray, ITGA9 and WNT7A could be validated. 5'-aza-2' deoxycytidine treatment restored the expression of ITGA9 and WNT7A in two NPC cell lines...
October 13, 2015: Oncotarget
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