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Dickkopf AND Neural

Z Malik, M Alexiou, B Hallgrimsson, A N Economides, H U Luder, D Graf
Formation of highly organized dental hard tissues is a complex process involving sequential and ordered deposition of an extracellular scaffold, followed by its mineralization. Odontoblast and ameloblast differentiation involves reciprocal and sequential epithelial-mesenchymal interactions. Similar to early tooth development, various Bmps are expressed during this process, although their functions have not been explored in detail. Here, we investigated the role of odontoblast-derived Bmp2 for tooth mineralization using Bmp2 conditional knockout mice...
February 1, 2018: Journal of Dental Research
Frederik Ziebell, Sascha Dehler, Ana Martin-Villalba, Anna Marciniak-Czochra
New neurons are continuously generated in the dentate gyrus of the adult hippocampus. This continuous supply of newborn neurons is important to modulate cognitive functions. Yet the number of newborn neurons declines with age. Increasing Wnt activity upon loss of dickkopf 1 can counteract both the decline of newborn neurons and the age-related cognitive decline. However, the precise cellular changes underlying the age-related decline or its rescue are fundamentally not understood. The present study combines a mathematical model and experimental data to address features controlling neural stem cell (NSC) dynamics...
January 8, 2018: Development
Jing Zhang, Nan Kang, Xiaotong Yu, Yuewen Ma, Xining Pang
Neural stem cell (NSC) proliferation and differentiation play a pivotal role in the repair of brain function in central nervous system (CNS) diseases. Radial extracorporeal shock wave therapy (rESWT) is a non-invasive and innovative treatment for many conditions, yet little is known about the effects of this treatment on NSCs. Mouse NSCs (NE-4C) were exposed to rESWT with 1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 bar (500 impulses, and 2 Hz) in vitro. Cell viability test results indicated that rESWT, at a dose of 2...
November 10, 2017: Scientific Reports
YunLong Xu, Fen He, FangFang Qi, Guangqi Yang, FuXiang Zheng, JunHua Yang, Xiao Wang, JunXiu Liu, JunTao Zou
Neonatal Bacillus Calmette-Guérin (BCG) vaccination results in a positive effect on hippocampal neurogenesis and cognition. Serum cytokines are considered to be the chief culprit. In this study, serum from BCG-treated mice was identified as Th1 polarized serum. The serum showed an increased ratio of IFN-γ to IL-4 and decreased levels of TNF-α and IL-6. After Th1 polarized serum was injected intraperitoneally into postnatal mice, the levels of cytokines and ratio of IFN-γ to IL-4 in the serum and hippocampus of postnatal mice showed a similar alteration as those in Th1 polarized serum...
March 22, 2017: Neurobiology of Learning and Memory
Anne-Li Lind, Payam Emami Khoonsari, Marcus Sjödin, Lenka Katila, Magnus Wetterhall, Torsten Gordh, Kim Kultima
OBJECTIVES: Electrical neuromodulation by spinal cord stimulation (SCS) is a well-established method for treatment of neuropathic pain. However, the mechanism behind the pain relieving effect in patients remains largely unknown. In this study, we target the human cerebrospinal fluid (CSF) proteome, a little investigated aspect of SCS mechanism of action. METHODS: Two different proteomic mass spectrometry protocols were used to analyze the CSF of 14 SCS responsive neuropathic pain patients...
August 2016: Neuromodulation: Journal of the International Neuromodulation Society
Sudha Warrier, Raja Marimuthu, Sreeja Sekhar, G Bhuvanalakshmi, Frank Arfuso, Anjan Kumar Das, Ramesh Bhonde, Ralph Martins, Arun Dharmarajan
The extracellular ligand, Wnt, and its receptors are involved in sign al transduction and play an important role in axis formation and neural development. In neurodegenerative disorders such as Alzheimer's disease (AD), a decrease of the intracellular Wnt effector, β-catenin, has been linked to amyloid-β-peptide-induced neurotoxicity. Despite this knowledge, targeting Wnt inhibitors as potential biomarkers has not been explored, and harnessing Wnt activators as therapeutic candidates remains largely not investigated...
June 2016: International Journal of Biochemistry & Cell Biology
Yoshiyasu Fukusumi, Florian Meier, Sebastian Götz, Friederike Matheus, Martin Irmler, Ruth Beckervordersandforth, Theresa Faus-Kessler, Eleonora Minina, Benedict Rauser, Jingzhong Zhang, Ernest Arenas, Elisabet Andersson, Christof Niehrs, Johannes Beckers, Antonio Simeone, Wolfgang Wurst, Nilima Prakash
Wingless-related MMTV integration site 1 (WNT1)/β-catenin signaling plays a crucial role in the generation of mesodiencephalic dopaminergic (mdDA) neurons, including the substantia nigra pars compacta (SNc) subpopulation that preferentially degenerates in Parkinson's disease (PD). However, the precise functions of WNT1/β-catenin signaling in this context remain unknown. Stem cell-based regenerative (transplantation) therapies for PD have not been implemented widely in the clinical context, among other reasons because of the heterogeneity and incomplete differentiation of the transplanted cells...
September 30, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Hisayuu Shindoh, Hidetaka Okada, Tomoko Tsuzuki, Akemi Nishigaki, Hideharu Kanzaki
OBJECTIVE: To investigate the role of heart and neural crest derivatives-expressed transcript 2 (HAND2) during decidualization of human endometrial stromal cells (ESCs). DESIGN: In vitro experiment. SETTING: Research laboratory. PATIENT(S): Twenty-six patients undergoing hysterectomy for benign reasons. INTERVENTION(S): ESCs were cultured for 12 days with HAND2 small interfering RNA (siRNA) or nonsilencing RNA during decidualization by medroxyprogesterone acetate (MPA) and E2...
June 2014: Fertility and Sterility
Carolin Mußmann, Rayk Hübner, Michaela Trilck, Arndt Rolfs, Moritz J Frech
Human neural stem/progenitor cell (hNPC)-derived neuronal progeny has been suggested as a promising cell source in a variety of neurodegenerative diseases. Understanding the underlying mechanisms that regulate neuronal differentiation is essential for efficient cell-based therapies. Wnt and Notch signaling has been shown to be crucial in this process. However, their interactions in the process of neuronal differentiation remain elusive. By using human fetal (ReNcell VM) and iPS-derived hNPCs we demonstrate that Wnt-3a immediately induced a transient HES1 upregulation and a sustained HES5 repression that was accompanied by upregulation of the proneural gene MASH1...
June 15, 2014: Stem Cells and Development
Insik Hwang, Ju-Hwang Park, Hang-Soo Park, Kyung-Ah Choi, Ki-Cheon Seol, Seung-Ick Oh, Seongman Kang, Sunghoi Hong
BACKGROUND: Melanin for skin pigmentation is synthesized from tyrosine via an enzymatic cascade that is controlled by tyrosinase (TYR), tyrosinase-related protein 1 (TRP1), and dopachrome tautomerase/tyrosinase related protein 2 (Dct/TRP2), which are the targets of microphthalmia-associated transcription factor (MITF). MITF is a master regulator of pigmentation and a target of β-catenin in Wnt/β-catenin signaling during melanocyte differentiation. Stem cells have been used in skin pigmentation studies, but the mechanisms were not determined for the conditioned medium (CM)-mediated effects...
December 2013: Journal of Dermatological Science
Désirée R M Seib, Nina S Corsini, Kristina Ellwanger, Christian Plaas, Alvaro Mateos, Claudia Pitzer, Christof Niehrs, Tansu Celikel, Ana Martin-Villalba
Memory impairment has been associated with age-related decline in adult hippocampal neurogenesis. Although Notch, bone morphogenetic protein, and Wnt signaling pathways are known to regulate multiple aspects of adult neural stem cell function, the molecular basis of declining neurogenesis in the aging hippocampus remains unknown. Here, we show that expression of the Wnt antagonist Dickkopf-1 (Dkk1) increases with age and that its loss enhances neurogenesis in the hippocampus. Neural progenitors with inducible loss of Dkk1 increase their Wnt activity, which leads to enhanced self-renewal and increased generation of immature neurons...
February 7, 2013: Cell Stem Cell
Jianli Shi, Huarong Zhang, Robin D Dowell, Michael W Klymkowsky
Studies on the role of the E-box binding transcription factor Snail2 (Slug) in the induction of neural crest by mesoderm (Shi et al., 2011) revealed an unexpected increase in the level of sizzled RNA in the dorsolateral mesodermal zone (DMLZ) of morphant Xenopus embryos. sizzled encodes a secreted protein with both Wnt and BMP inhibitor activities. Morpholino-mediated down-regulation of sizzled expression in one cell of two cell embryos or the C2/C3 blastomeres of 32-cell embryos, which give rise to the DLMZ, revealed decreased expression of the mesodermal marker brachyury and subsequent defects in neural crest induction, pronephros formation, and muscle patterning...
March 15, 2012: Biology Open
Erin L Scott, Quan-Guang Zhang, Dong Han, Bhavna N Desai, Darrell W Brann
Surgically menopausal women incur a 2- to 5-fold increased risk for dementia and mortality from neurological diseases, but the mechanisms underlying these increased risks remain unclear. Previously, we demonstrated that after global cerebral ischemia (GCI), 17β-estradiol (E2 or estrogen) suppresses hippocampal elevation of the Wnt antagonist Dickkopf-1 (Dkk1), a neurodegenerative factor. We, thus, hypothesized that prolonged loss of E2 may lead to dysregulation of neural Dkk1 and Wnt/β-Catenin signaling, which could contribute to an increased risk of neurodegeneration...
June 2013: Steroids
Rajesh Ramachandran, Xiao-Feng Zhao, Daniel Goldman
In zebrafish, retinal injury stimulates Müller glia (MG) reprograming, allowing them to generate multipotent progenitors that replace damaged cells and restore vision. Recent studies suggest that transcriptional repression may underlie these events. To identify transcriptional repressors, we compared the transcriptomes of MG and MG-derived progenitors and identified insm1a, a repressor exhibiting a biphasic pattern of expression that is essential for retina regeneration. Insm1a was found to suppress ascl1a and its own expression, and link injury-dependent ascl1a induction with the suppression of the Wnt inhibitor dickkopf (dkk), which is necessary for MG dedifferentiation...
October 2012: Nature Cell Biology
Dustin Hambright, Kye-Yoon Park, Matthew Brooks, Ron McKay, Anand Swaroop, Igor O Nasonkin
PURPOSE: To examine the potential of NIH-maintained human embryonic stem cell (hESC) lines TE03 and UC06 to differentiate into retinal progenitor cells (hESC-RPCs) using the noggin/Dkk-1/IGF-1/FGF9 protocol. An additional goal is to examine the in vivo dynamics of maturation and retinal integration of subretinal and epiretinal (vitreous space) hESC-RPC grafts without immunosuppression. METHODS: hESCs were neuralized in vitro with noggin for 2 weeks and expanded to derive neuroepithelial cells (hESC-neural precursors, NPs)...
2012: Molecular Vision
Ayumi Miyake, Satoka Nihno, Yuino Murakoshi, Ayano Satsuka, Yoshiaki Nakayama, Nobuyuki Itoh
Wnt signaling plays crucial roles in neural development. We previously identified Neucrin, a neural-specific secreted antagonist of canonical Wnt/β-catenin signaling, in humans and mice. Neucrin has one cysteine-rich domain, in which the positions of 10 cysteine residues are similar to those in the second cysteine-rich domain of Dickkopfs, secreted Wnt antagonists. Here, we have identified zebrafish neucrin to understand its roles in vivo. Zebrafish Neucrin also has one cysteine-rich domain, which is significantly similar to that of mouse Neucrin...
January 2012: Mechanisms of Development
Michaela Moors, Raj Bose, Krishan Johansson-Haque, Karin Edoff, Sam Okret, Sandra Ceccatelli
Glucocorticoids (GC) are critical for normal development of the fetal brain, and alterations in their levels can induce neurotoxicity with detrimental consequences. Still, there is little information available on the effects of GC on human neural stem/progenitor cells (hNPC). In the present study, we have investigated the effects of the synthetic GC dexamethasone (Dex) on hNPC grown as neurospheres, with special focus on their proliferation and differentiation capacity and the underlying molecular mechanisms...
February 2012: Toxicological Sciences: An Official Journal of the Society of Toxicology
Noriyuki Nishimura, Tri Budi Hartomo, Thi Van Huyen Pham, Myeong Jin Lee, Tomoto Yamamoto, Satoru Morikawa, Daiichiro Hasegawa, Hiroki Takeda, Keiichiro Kawasaki, Yoshiyuki Kosaka, Nobuyuki Yamamoto, Ikuko Kubokawa, Takeshi Mori, Tomoko Yanai, Akira Hayakawa, Yasuhiro Takeshima, Kazumoto Iijima, Masafumi Matsuo, Hisahide Nishio
OBJECTIVES: A growing number of epidemiological studies have demonstrated that the consumption of green tea inhibits the growth of a variety of cancers. Epigallocatechin gallate (EGCG), the most abundant catechin in green tea, has been shown to have an anti-cancer effect against many cancers. Most cancers are believed to be initiated from and maintained by a small population of tumor-initiating cells (TICs) that are responsible for chemotherapeutic resistance and tumor relapse. In neuroblastoma, an aggressive pediatric tumor that often relapses and has a poor prognosis, TICs were recently identified as spheres grown in a serum-free non-adherent culture used for neural crest stem cell growth...
May 2012: Environmental Health and Preventive Medicine
Minako Ogata-Iwao, Masaru Inatani, Keiichiro Iwao, Yuji Takihara, Yuko Nakaishi-Fukuchi, Fumitoshi Irie, Shigeru Sato, Takahisa Furukawa, Yu Yamaguchi, Hidenobu Tanihara
PURPOSE. Heparan sulfate (HS) is abundantly expressed in the developing neural retina; however, its role in the intraretinal axon guidance of retinal ganglion cells (RGCs) remains unclear. In this study, the authors examined whether HS was essential for the axon guidance of RGCs toward the optic nerve head. METHODS. The authors conditionally ablated the gene encoding the exostosin-1 (Ext1) enzyme, using the dickkopf homolog 3 (Dkk3)-Cre transgene, which disrupted HS expression in the mouse retina during directed pathfinding by RGC axons toward the optic nerve head...
August 2011: Investigative Ophthalmology & Visual Science
Jing Xu, Hao Wang, Tao Liang, Xiangsheng Cai, Xiurong Rao, Zhenbo Huang, Guoqing Sheng
Retinoic acid (RA) plays multiple roles in the nervous system, including induction of neural differentiation, axon outgrowth and neural patterning. Previously, RA for neural differentiation of embryonic stem (ES) cells always relies on embryoid bodies (EBs) formation. Here we report an in vitro adherent monoculture system to induce mouse ES cells into neural cells accompanied with RA. RA (1 μM) treatment, during initial 2 days of differentiation, can enhance the expression of neural markers, such as Nestin, Tuj1 and MAP2, and result in an earlier neural differentiation of ES cells...
February 2012: Molecular Biology Reports
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