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Sanjiv Neupane, Wern-Joo Sohn, Gi-Jeong Gwon, Ki-Rim Kim, Sanggyu Lee, Chang-Hyeon An, Jo-Young Suh, Hong-In Shin, Hitoshi Yamamoto, Sung-Won Cho, Youngkyun Lee, Jae-Young Kim
Adenomatosis polyposis coli downregulated 1 (APCDD1), a negative regulator of Wnt signaling, was examined to understand detailed mechanisms underlying Wnt signaling tooth development. In situ hybridization showed that Apcdd1 was expressed in the condensed mesenchyme at the bud stage, and in the inner enamel epithelium (IEE), including enamel knot (EK) at the cap stage. In vitro organ cultivation by using Apcdd1 antisense oligodeoxynucleotides was performed at E13.5 for 2 days to define the developmental functions of APCDD1 during tooth development...
October 2015: Histochemistry and Cell Biology
Hyun Kyoung Lee, Dylan Laug, Wenyi Zhu, Jay M Patel, Kevin Ung, Benjamin R Arenkiel, Stephen P J Fancy, Carrie Mohila, Benjamin Deneen
Wnt signaling plays an essential role in developmental and regenerative myelination of the CNS, therefore it is critical to understand how the factors associated with the various regulatory layers of this complex pathway contribute to these processes. Recently, Apcdd1 was identified as a negative regulator of proximal Wnt signaling, however its role in oligodendrocyte (OL) differentiation and reymelination in the CNS remain undefined. Analysis of Apcdd1 expression revealed dynamic expression during OL development, where its expression is upregulated during differentiation...
October 2015: Glia
S Viale-Bouroncle, C Klingelhöffer, T Ettl, C Morsczeck
In hair follicle cells APCDD1 inhibits the canonical WNT/β-Catenin pathway and its inactivation is associated with an autosomal dominant form of hair loss. We analyzed the role of APCDD1 for the osteogenic differentiation in dental follicle cells (DFCs) and identified a new and surprising function. Contrarily to hair follicle cells APCDD1 was crucial for the expression of β-Catenin and for the activity of the TCF/LEF reporter assay in DFCs. In addition, a depletion of APCDD1 inhibits the expression of osteogenic markers such as RUNX2 and decreased the matrix mineralization...
February 13, 2015: Biochemical and Biophysical Research Communications
R C Betz
The monogenic inherited isolated alopecias comprise a group of clinically and genetically heterogeneous disorders with decreased or absent hair. Clinical classification of the isolated alopecias is based upon the onset of the disorder, the regions affected, and the structure of the hair shaft. Men and women are equally affected, and the mode of inheritance is autosomal dominant or autosomal recessive. Therapy does not exist for these rare forms of alopecia. However, molecular genetic diagnosis is possible for the identification of the genetic causes and for the specification of the recurrence risk...
June 2014: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
Qinghang Meng, Chang Jin, Yinglei Chen, Jing Chen, Mario Medvedovic, Ying Xia
Closure of an epithelium opening is a critical morphogenetic event for development. An excellent example for this process is the transient closure of embryonic eyelid. Eyelid closure requires shape change and migration of epithelial cells at the tip of the developing eyelids, and is dictated by numerous signaling pathways. Here we evaluated gene expression in epithelial cells isolated from the tip (leading edge, LE) and inner surface epithelium (IE) of the eyelid from E15.5 mouse fetuses by laser capture microdissection (LCM)...
2014: PloS One
Kei Kamide, Kei Asayama, Tomohiro Katsuya, Takayoshi Ohkubo, Takuo Hirose, Ryusuke Inoue, Hirohito Metoki, Masahiro Kikuya, Taku Obara, Hironori Hanada, Lutgarde Thijs, Tatiana Kuznetsova, Yuichi Noguchi, Ken Sugimoto, Mitsuru Ohishi, Shigeto Morimoto, Takeshi Nakahashi, Shin Takiuchi, Toshihiko Ishimitsu, Takuya Tsuchihashi, Masayoshi Soma, Jitsuo Higaki, Hideo Matsuura, Tatsuo Shinagawa, Toshiyuki Sasaguri, Tetsuro Miki, Kazuo Takeda, Kazuaki Shimamoto, Michio Ueno, Naohisa Hosomi, Jyouji Kato, Norio Komai, Shunichi Kojima, Kazuhiro Sase, Toshiyuki Miyata, Hitonobu Tomoike, Yuhei Kawano, Toshio Ogihara, Hiromi Rakugi, Jan A Staessen, Yutaka Imai
BACKGROUND: Patients with mild-to-moderate essential hypertension in the HOMED-BP trial were randomly allocated to first-line treatment with a calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB). METHODS: We recruited 265 (93 for CCB, 71 for ACEI and 101 for ARB) patients who completed the genomic study. Home blood pressure was measured for 5 days off-treatment before randomization and for 5 days after 2-4 weeks of randomized drug treatment...
November 2013: Pharmacogenomics
Mujib Ullah, Stefan Stich, Thomas Häupl, Jan Eucker, Michael Sittinger, Jochen Ringe
BACKGROUND: During mesenchymal stem cell (MSC) conversion into adipocytes, the adipogenic cocktail consisting of insulin, dexamethasone, indomethacin and 3-isobutyl-1-methylxanthine not only induces adipogenic-specific but also genes for non-adipogenic processes. Therefore, not all significantly expressed genes represent adipogenic-specific marker genes. So, our aim was to filter only adipogenic-specific out of all expressed genes. We hypothesize that exclusively adipogenic-specific genes change their expression during adipogenesis, and reverse during dedifferentiation...
2013: PloS One
Cristina-Maria Cruciat, Christof Niehrs
Signaling by the Wnt family of secreted glycoproteins plays important roles in embryonic development and adult homeostasis. Wnt signaling is modulated by a number of evolutionarily conserved inhibitors and activators. Wnt inhibitors belong to small protein families, including sFRP, Dkk, WIF, Wise/SOST, Cerberus, IGFBP, Shisa, Waif1, APCDD1, and Tiki1. Their common feature is to antagonize Wnt signaling by preventing ligand-receptor interactions or Wnt receptor maturation. Conversely, the Wnt activators, R-spondin and Norrin, promote Wnt signaling by binding to Wnt receptors or releasing a Wnt-inhibitory step...
March 2013: Cold Spring Harbor Perspectives in Biology
Peng Kang, Hyun Kyoung Lee, Stacey M Glasgow, Meggie Finley, Tataka Donti, Zachary B Gaber, Brett H Graham, Aaron E Foster, Bennett G Novitch, Richard M Gronostajski, Benjamin Deneen
Transcriptional cascades that operate over the course of lineage development are fundamental mechanisms that control cellular differentiation. In the developing central nervous system (CNS), these mechanisms are well characterized during neurogenesis, but remain poorly defined during neural stem cell commitment to the glial lineage. NFIA is a transcription factor that plays a crucial role in the onset of gliogenesis; we found that its induction is regulated by the transcription factor Sox9 and that this relationship mediates the initiation of gliogenesis...
April 12, 2012: Neuron
S K Baniwal, P K Shah, Y Shi, J H Haduong, Y A Declerck, Y Gabet, B Frenkel
UNLABELLED: We profiled the global gene expression of a bone marrow-derived mesenchymal pluripotent cell line in response to Runx2 expression. Besides osteoblast differentiation, Runx2 promoted the osteoclastogenesis of co-cultured splenocytes. This was attributable to the upregulation of many novel osteoclastogenic genes and the downregulation of anti-osteoclastogenic genes. INTRODUCTION: In addition to being a master regulator for osteoblast differentiation, Runx2 controls osteoblast-driven osteoclastogenesis...
April 2012: Osteoporosis International
Myung-Ju Ahn, Hong-Hee Won, Jeeyun Lee, Seung-Tae Lee, Jong-Mu Sun, Yeon Hee Park, Jin Seok Ahn, O Jung Kwon, Hojoong Kim, Young Mog Shim, Jhingook Kim, Kwhanmien Kim, Yeul Hong Kim, Jae Yong Park, Jong-Won Kim, Keunchil Park
The proportion of never smoker non-small cell lung cancer (NSCLC) in Asia is about 30-40%. Despite the striking demographics and high prevalence of never smoker NSCLC, the exact causes still remain undetermined. Although several genome wide association (GWA) studies were conducted to find susceptibility loci for lung cancer in never smokers, no regions were replicated except for 5p15.33, suggesting locus heterogeneity and different environmental toxic effects. To identify genetic loci associated with susceptibility of lung cancer in never smokers, we performed a GWA analysis using the Affymetrix 6...
March 2012: Human Genetics
Dana W Y Tsui, Y M Doris Lam, Wing S Lee, Tak Y Leung, Tze K Lau, Elizabeth T Lau, Mary H Y Tang, Ranjit Akolekar, Kypros H Nicolaides, Rossa W K Chiu, Y M Dennis Lo, Stephen S C Chim
BACKGROUND: Noninvasive prenatal diagnosis of fetal aneuploidy by maternal plasma analysis is challenging owing to the low fractional and absolute concentrations of fetal DNA in maternal plasma. Previously, we demonstrated for the first time that fetal DNA in maternal plasma could be specifically targeted by epigenetic (DNA methylation) signatures in the placenta. By comparing one such methylated fetal epigenetic marker located on chromosome 21 with another fetal genetic marker located on a reference chromosome in maternal plasma, we could infer the relative dosage of fetal chromosome 21 and noninvasively detect fetal trisomy 21...
2010: PloS One
Yutaka Shimomura, Dritan Agalliu, Alin Vonica, Victor Luria, Muhammad Wajid, Alessandra Baumer, Serena Belli, Lynn Petukhova, Albert Schinzel, Ali H Brivanlou, Ben A Barres, Angela M Christiano
Hereditary hypotrichosis simplex is a rare autosomal dominant form of hair loss characterized by hair follicle miniaturization. Using genetic linkage analysis, we mapped a new locus for the disease to chromosome 18p11.22, and identified a mutation (Leu9Arg) in the adenomatosis polyposis down-regulated 1 (APCDD1) gene in three families. We show that APCDD1 is a membrane-bound glycoprotein that is abundantly expressed in human hair follicles, and can interact in vitro with WNT3A and LRP5-two essential components of Wnt signalling...
April 15, 2010: Nature
Birgit Zirn, Birgit Samans, Stefanie Wittmann, Thorsten Pietsch, Ivo Leuschner, Norbert Graf, Manfred Gessler
The WNT/beta-catenin pathway is involved in numerous human cancers. Mutations of the CTNNB1 (beta-catenin) gene have also been detected in a subset of pediatric Wilms tumors, but the target genes of the deregulated WNT/beta-catenin pathway in these tumors have yet to be identified. To compare gene expression profiles of Wilms tumors with and without mutations of CTNNB1, we used 11.5-k cDNA microarrays. Most of the tumors (86%) had received preoperative chemotherapy as mandated by the European SIOP protocol...
June 2006: Genes, Chromosomes & Cancer
Kyung-Tai Lee, Eung-Woo Park, Sunjin Moon, Hye-Sook Park, Hyung-Yong Kim, Gil-Won Jang, Bong-Hwan Choi, H Y Chung, Ji-Woong Lee, Il-Cheong Cheong, Sung-Jong Oh, Heebal Kim, Dong-Sang Suh, Tae-Hun Kim
On pig chromosome 6, the SW71 microsatellite is located in the region corresponding to several quantitative trait loci (QTL), such as those for intramuscular fat content and for body weight at 4 weeks of age. The genomic sequence of approximately 909 kb was obtained from seven BAC clones encompassing the SW71 region corresponding to human 18q11.21-q11.22. By searching the NCBI GenBank using BLASTX and BLASTN, this 909-kb segment was found to contain eight genes, RAB31, TXNDC2, VAPA, APCDD1, NAPG, FAM38B, C18orf30, and C18orf58, and one putative gene (DN119777)...
February 2006: Genomics
Shigehiro Kuraku, Ryo Usuda, Shigeru Kuratani
The turtle shell is an evolutionary novelty in which the developmental pattern of the ribs is radically modified. In contrast to those of other amniotes, turtle ribs grow laterally into the dorsal dermis to form a carapace. The lateral margin of carapacial primordium is called the carapacial ridge (CR), and is thought to play an essential role in carapace patterning. To reveal the developmental mechanisms underlying this structure, we systematically screened for genes expressed specifically in the CR of the Chinese soft-shelled turtle, Pelodiscus sinensis, using microbead-based differential cDNA analysis and real-time reverse transcription-polymerase chain reaction...
January 2005: Evolution & Development
Tomi Jukkola, Natalia Sinjushina, Juha Partanen
We identified the mouse homolog of human DRAPC1 (APCDD1) gene, shown to be a target of Wnt/beta-catenin signaling pathway in cancer cell lines. Analysis of its spatiotemporal expression in mouse embryos from E7.5 to E14 showed that Drapc1 is expressed during development of the extraembryonic structures, nervous system, vascular system and inner ear. In addition, Drapc1 is expressed in the mesenchyme of several developing organs at sites of epithelio-mesenchymal interactions. Drapc1 expression was also found in the hair follicles of the adult mouse skin...
October 2004: Gene Expression Patterns: GEP
Meiko Takahashi, Manabu Fujita, Yoichi Furukawa, Ryuji Hamamoto, Takashi Shimokawa, Nobutomo Miwa, Michio Ogawa, Yusuke Nakamura
To clarify the molecular mechanisms of human carcinogenesis associated with abnormal beta-catenin/T-cell factor (Tcf) signaling, we have been using cDNA microarrays to search for genes whose expression is significantly altered after introduction of wild-type APC into SW480 colon cancer cells. These experiments identified a novel human gene, termed APCDD1, that was down-regulated in the cancer cells by exogenous wild-type APC; its expression was also reduced in response to transduction of AXIN1. Moreover, we documented elevated expression of APCDD1 in 18 of 27 primary colon cancer tissues compared with corresponding noncancerous mucosae...
October 15, 2002: Cancer Research
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