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Yanhan Huang, Jennifer Hill, Andrew Yatteau, Loksum Wong, Tao Jiang, Jelena Petrovic, Lin Gan, Lijin Dong, Doris K Wu
LIM-domain containing transcription factors (LIM-TFs) are conserved factors important for embryogenesis. The specificity of these factors in transcriptional regulation is conferred by the complexes they form with other proteins such as LIM-domain-binding (Ldb) proteins and LIM-domain only (LMO) proteins. Unlike LIM-TF, these proteins do not bind DNA directly. LMO are negative regulators of LIM-TF and they function by competing with LIM-TFs for binding to Ldbs. Although the LIM-TF Lmx1a is expressed in the developing mouse hindbrain, which provides many of the extrinsic signals for inner ear formation, conditional knockout embryos of both sexes show that the inner ear source of Lmx1a is the major contributor of ear patterning...
May 16, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Keshuo Ding, Zhengsheng Wu, Xiaocan Li, Youjing Sheng, Xiaonan Wang, Sheng Tan
Breast cancer is the leading cause of cancer-related mortality in women worldwide. Trastuzumab (Herceptin) is an effective antibody drug for HER2 positive breast cancer; de novo or acquired trastuzumab resistance retarded the use of trastuzumab for at least 70% of HER2 positive breast cancers. In this study, we reported LMO4 (a member of LIM-only proteins) promoted trastuzumab resistance in human breast cancer cells. Over-expression of LMO4 was observed in acquired trastuzumab resistance breast cancer cells SKBR3 HR and BT474 HR...
2018: American Journal of Cancer Research
Zhenzhen Tu, Siping Zhang, Guoling Zhou, Lili Zhou, Qiantong Xiang, Qiongqiong Chen, Pan Zhao, Heqin Zhan, Haisheng Zhou, Liangdan Sun
Psoriasis is an autoimmune disease characterized by abnormal differentiation and hyperproliferation of epidermal keratinocytes. LIM-domain only protein 4 (LMO4) is a transcription factor coregulator that promotes the assembly of multiprotein complexes to regulate mammary epithelium and keratinocyte differentiation and proliferation during embryogenesis. In this study, LMO4 has been found to be abundantly expressed in psoriatic epidermis. LMO4 expression is increased in human keratinocytes induced to differentiate by calcium ex vivo, and LMO4 overexpression induces spontaneous differentiation and growth acceleration of human keratinocytes in the absence of calcium...
December 16, 2017: Journal of Investigative Dermatology
Rajamani Rathinam, Rita Rosati, Samson Jamesdaniel
Lim-domain only 4 (LMO4) plays a critical role in mediating the ototoxic side-effects of cisplatin, a highly effective anti-cancer drug. However, the signaling mechanism by which cochlear LMO4 mediates otopathology is yet to be fully understood. Knockout cell culture models are useful tools for investigating the functional roles of novel genes and delineating associated signaling pathways. Therefore, LMO4 knockout organ of Corti cells were generated by using the CRISPR (clustered regularly interspersed short palindromic repeats)/Cas9 (CRISPR-associated protein 9) system...
April 2018: Journal of Cellular Biochemistry
Sung Young Park, Sang-Ho Song, Brandon Palmateer, Akash Pal, Eric D Petersen, Gabrielle P Shall, Ryan M Welchko, Keiji Ibata, Atsushi Miyawaki, George J Augustine, Ute Hochgeschwender
Previous work has demonstrated that fusion of a luciferase to an opsin, to create a luminescent opsin or luminopsin, provides a genetically encoded means of manipulating neuronal activity via both chemogenetic and optogenetic approaches. Here we have expanded and refined the versatility of luminopsin tools by fusing an alternative luciferase variant with high light emission, Gaussia luciferase mutant GLucM23, to depolarizing and hyperpolarizing channelrhodopsins with increased light sensitivity. The combination of GLucM23 with Volvox channelrhodopsin-1 produced LMO4, while combining GLucM23 with the anion channelrhodopsin iChloC yielded iLMO4...
September 1, 2017: Journal of Neuroscience Research
Madalynn Erb, Bora Lee, So Yeon Seo, Jae W Lee, Seunghee Lee, Soo-Kyung Lee
Motor neuron (MN) progenitor cells rapidly induce high expression of the transcription factors Islet-1 (Isl1), LIM-homeobox 3 (Lhx3), and the transcriptional regulator LMO4, as they differentiate. While these factors are critical for MN specification, the mechanisms regulating their precise temporal and spatial expression patterns are not well characterized. Isl1 and Lhx3 form the Isl1-Lhx3 complex, which induces the transcription of genes critical for MN specification and maturation. Here, we report that Isl1 , Lhx3 , and Lmo4 are direct target genes of the Isl1-Lhx3 complex...
March 2017: ENeuro
Lene C Olsen, Kally C O'Reilly, Nina B Liabakk, Menno P Witter, Pål Sætrom
The medial entorhinal cortex (MEC) is important in spatial navigation and memory formation and its layers have distinct neuronal subtypes, connectivity, spatial properties, and disease susceptibility. As little is known about the molecular basis for the development of these laminar differences, we analyzed microRNA (miRNA) and messenger RNA (mRNA) expression differences between rat MEC layer II and layers III-VI during postnatal development. We identified layer and age-specific regulation of gene expression by miRNAs, which included processes related to neuron specialization and locomotor behavior...
September 2017: Brain Structure & Function
David J Duffy, Aleksandar Krstic, Melinda Halasz, Thomas Schwarzl, Anja Konietzny, Kristiina Iljin, Desmond G Higgins, Walter Kolch
BACKGROUND: Retinoid therapy is widely employed in clinical oncology to differentiate malignant cells into their more benign counterparts. However, certain high-risk cohorts, such as patients with MYCN-amplified neuroblastoma, are innately resistant to retinoid therapy. Therefore, we employed a precision medicine approach to globally profile the retinoid signalling response and to determine how an excess of cellular MYCN antagonises these signalling events to prevent differentiation and confer resistance...
February 10, 2017: Genome Medicine
Wenjun Wang, Sipei Wu, Minzhang Guo, Jianxing He
BACKGROUND: The aims of this study were to analyze the association of LMO4 with non-small-cell lung cancer (NSCLC) survival rate, and to determine its functional role and signaling pathway in lung cancer. METHODS: Immunohistochemistry (IHC) was used to detect the expression of LMO4 in NSCLC cell lines and tumor tissues. Migration and invasion ability was detected respectively by wound healing test and transwell test. Immunofluorescence and western blot were detected of AKT/PI3K pathway related genes MAPK, PI3K, AKT...
December 2016: Journal of Thoracic Disease
Samson Jamesdaniel, Rajamani Rathinam, William L Neumann
Cisplatin-induced ototoxicity remains a primary dose-limiting adverse effect of this highly effective anticancer drug. The clinical utility of cisplatin could be enhanced if the signaling pathways that regulate the toxic side-effects are delineated. In previous studies, we reported cisplatin-induced nitration of cochlear proteins and provided the first evidence for nitration and downregulation of cochlear LIM domain only 4 (LMO4) in cisplatin ototoxicity. Here, we extend these findings to define the critical role of nitrative stress in cisplatin-induced downregulation of LMO4 and its consequent ototoxic effects in UBOC1 cell cultures derived from sensory epithelial cells of the inner ear and in CBA/J mice...
December 2016: Redox Biology
Elizabeth A Simonik, Ying Cai, Katherine N Kimmelshue, Dana M Brantley-Sieders, Holli A Loomans, Claudia D Andl, Grant M Westlake, Victoria M Youngblood, Jin Chen, Wendell G Yarbrough, Brandee T Brown, Lalitha Nagarajan, Stephen J Brandt
Squamous cell carcinoma of the head and neck (HNSCC) accounts for more than 300,000 deaths worldwide per year as a consequence of tumor cell invasion of adjacent structures or metastasis. LIM-only protein 4 (LMO4) and LIM-domain binding protein 1 (LDB1), two directly interacting transcriptional adaptors that have important roles in normal epithelial cell differentiation, have been associated with increased metastasis, decreased differentiation, and shortened survival in carcinoma of the breast. Here, we implicate two LDB1-binding proteins, single-stranded binding protein 2 (SSBP2) and 3 (SSBP3), in controlling LMO4 and LDB1 protein abundance in HNSCC and in regulating specific tumor cell functions in this disease...
2016: PloS One
Mi-Ryung Han, Jirong Long, Ji-Yeob Choi, Siew-Kee Low, Sun-Seog Kweon, Ying Zheng, Qiuyin Cai, Jiajun Shi, Xingyi Guo, Keitaro Matsuo, Motoki Iwasaki, Chen-Yang Shen, Mi Kyung Kim, Wanqing Wen, Bingshan Li, Atsushi Takahashi, Min-Ho Shin, Yong-Bing Xiang, Hidemi Ito, Yoshio Kasuga, Dong-Young Noh, Koichi Matsuda, Min Ho Park, Yu-Tang Gao, Hiroji Iwata, Shoichiro Tsugane, Sue K Park, Michiaki Kubo, Xiao-Ou Shu, Daehee Kang, Wei Zheng
Breast cancer is one of the most common malignancies among women worldwide. Genetic factors have been shown to play an important role in breast cancer aetiology. We conducted a two-stage genome-wide association study (GWAS) including 14 224 cases and 14 829 controls of East Asian women to search for novel genetic susceptibility loci for breast cancer. Single nucleotide polymorphisms (SNPs) in two loci were found to be associated with breast cancer risk at the genome-wide significance level. The first locus, represented by rs12118297 at 1p22...
August 1, 2016: Human Molecular Genetics
Kawssar Harb, Elia Magrinelli, Céline S Nicolas, Nikita Lukianets, Laura Frangeul, Mariel Pietri, Tao Sun, Guillaume Sandoz, Franck Grammont, Denis Jabaudon, Michele Studer, Christian Alfano
During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex...
January 27, 2016: ELife
Kangxin Jin, Dongchang Xiao, Bogi Andersen, Mengqing Xiang
Understanding the molecular basis by which distinct cell types are specified is a central issue in retinogenesis and retinal disease development. Here we examined the role of LIM domain only 4 (Lmo4) in retinal development using both gain-of-function and loss-of-function approaches. By immunostaining, Lmo4 was found to be expressed in mouse retina from E10.5 to mature stages. Retroviral delivery of Lmo4 into retinal progenitor cells could promote the amacrine, bipolar and Müller cell fates at the expense of photoreceptors...
August 2016: Developmental Neurobiology
P Banerjee, H Harada, N G Tassew, J Charish, D Goldschneider, V A Wallace, S Sugita, P Mehlen, P P Monnier
While a great deal of progress has been made in understanding the molecular mechanisms that regulate retino-tectal mapping, the determinants that target retinal projections to specific layers of the optic tectum remain elusive. Here we show that two independent RGMa-peptides, C- and N-RGMa, activate two distinct intracellular pathways to regulate axonal growth. C-RGMa utilizes a Leukemia-associated RhoGEF (LARG)/Rho/Rock pathway to inhibit axonal growth. N-RGMa on the other hand relies on ϒ-secretase cleavage of the intracellular portion of Neogenin to generate an intracellular domain (NeICD) that uses LIM-only protein 4 (LMO4) to block growth...
March 2016: Cell Death and Differentiation
Rajani Maiya, Regina A Mangieri, Richard A Morrisett, Ulrike Heberlein, Robert O Messing
The ability to use environmental cues to predict rewarding events is essential to survival. The basolateral amygdala (BLA) plays a central role in such forms of associative learning. Aberrant cue-reward learning is thought to underlie many psychopathologies, including addiction, so understanding the underlying molecular mechanisms can inform strategies for intervention. The transcriptional regulator LIM-only 4 (LMO4) is highly expressed in pyramidal neurons of the BLA, where it plays an important role in fear learning...
July 1, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Aliaksei Z Holik, Caitlin E Filby, Julie Pasquet, Kati Viitaniemi, John Ciciulla, Kate D Sutherland, Marie-Liesse Asselin-Labat
BACKGROUND: The lung is constantly exposed to environmental challenges and must rapidly respond to external insults. Mechanisms involved in the repair of the damaged lung involve expansion of different epithelial cells to repopulate the injured cellular compartment. However, factors regulating cell proliferation following lung injury remain poorly understood. Here we studied the role of the transcriptional regulator Lmo4 during lung development, in the regulation of adult lung epithelial cell proliferation following lung damage and in the context of oncogenic transformation...
June 7, 2015: Respiratory Research
Bo-Hye Kim, Han-Na Kim, Seung-Ju Roh, Mi Kyeong Lee, Sarah Yang, Seung Ku Lee, Yeon-Ah Sung, Hye Won Chung, Nam H Cho, Chol Shin, Joohon Sung, Hyung-Lae Kim
Personality is a determinant of behavior and lifestyle that is associated with health and human diseases. Despite the heritability of personality traits is well established, the understanding of the genetic contribution to personality trait variation is extremely limited. To identify genetic variants associated with each of the five dimensions of personality, we performed a genome-wide association (GWA) meta-analysis of three cohorts, followed by comparison of a family cohort. Personality traits were measured with the Revised NEO Personality Inventory for the five-factor model (FFM) of personality...
August 2015: Journal of Human Genetics
Rongpan Bai, Chunhua Weng, Haojie Dong, Siqi Li, Guangdi Chen, Zhengping Xu
Colorectal cancer (CRC) is one of the most common cancers worldwide and its metastasis accounts for the majority of deaths. However, the molecular mechanisms underlying CRC progression are not well characterized. In this study, we identified miR-409-3p as a tumor suppressor of CRC. MiR-409-3p expression was significantly downregulated in CRC tissue compared to adjacent non-tumor tissue, and reduced miR-409-3p expression was correlated with CRC metastasis. In vitro and in vivo studies revealed that miR-409-3p negatively regulated CRC metastatic capacities, including suppressing cancer cell migration, invasion and metastasis...
November 15, 2015: International Journal of Cancer. Journal International du Cancer
José L Ferran, Luis Puelles, John L R Rubenstein
The prosomeric model proposes that the hypothalamus is a rostral forebrain entity, placed ventral to the telencephalon and rostral to the diencephalon. Gene expression markers differentially label molecularly distinct dorsoventral progenitor domains, which represent continuous longitudinal bands across the hypothalamic alar and basal regions. There is also circumstantial support for a rostrocaudal subdivision of the hypothalamus into transverse peduncular (caudal) and terminal (rostral) territories (PHy, THy)...
2015: Frontiers in Neuroanatomy
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