Abstract:
:Convergent extension (CE) is a fundamental morphogenetic mechanism that underlies numerous processes in vertebrate development, and its disruption can lead to human congenital disorders such as neural tube closure defects. The dynamic, oriented cell intercalation during CE is regulated by a group of core proteins identified originally in flies to coordinate epithelial planar cell polarity (PCP). The existing model explains how core PCP proteins, including Van Gogh (Vang) and Dishevelled (Dvl), segregate into distinct complexes on opposing cell cortex to coordinate polarity among static epithelial cells. The action of core PCP proteins in the dynamic process of CE, however, remains an enigma. In this report, we show that Vangl2 (Vang-like 2) exerts dual positive and negative regulation on Dvl during CE in both the mouse and Xenopus. We find that Vangl2 binds to Dvl to cell-autonomously promote efficient Dvl plasma membrane recruitment, a pre-requisite for PCP activation. At the same time, Vangl2 inhibits Dvl from interacting with its downstream effector Daam1 (Dishevelled associated activator of morphogenesis 1), and functionally suppresses Dvl → Daam1 cascade during CE. Our finding uncovers Vangl2-Dvl interaction as a key bi-functional switch that underlies the central logic of PCP signaling during morphogenesis, and provides new insight into PCP-related disorders in humans.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Seo HS,Habas R,Chang C,Wang Jdoi
10.1093/hmg/ddx095subject
Has Abstractpub_date
2017-06-01 00:00:00pages
2053-2061issue
11eissn
0964-6906issn
1460-2083pii
3067487journal_volume
26pub_type
杂志文章abstract::The childhood motor neuron disease spinal muscular atrophy (SMA) results from reduced expression of the survival motor neuron (SMN) gene. Previous studies using in vitro model systems and lower organisms have suggested that low levels of Smn protein disrupt prenatal developmental processes in lower motor neurons, infl...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp506
更新日期:2010-02-01 00:00:00
abstract::The expansion of CAG.CTG trinucleotide repeats has been associated with an increasing number of human diseases. Once into the expanded disease-associated range, the repeats become dramatically unstable in the germline and also throughout the soma. Instability is expansion-biased, contributing towards the unusual genet...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.8.845
更新日期:2001-04-01 00:00:00
abstract::In studies of genomic imprinting in the Prader-Willi/Angelman domain, an agouti coat color cassette was inserted into the downstream open reading frame (ORF) of the imprinted bicistronic Snurf-Snrpn locus in the mouse. The fusion gene was maternally silenced, as is Snurf-Snrpn, and produced a tan abdomen only when inh...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.14.1659
更新日期:2002-07-01 00:00:00
abstract::Alterations in mitochondrial DNA (mtDNA) and consequent loss of mitochondrial function underlie the mitochondrial theory of aging. In this study, we systematically analyzed the mtDNA control region somatic mutation pattern in 2864 single hematopoietic stem cells (HSCs) and progenitors, isolated by flow cytometry sorti...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl457
更新日期:2007-02-01 00:00:00
abstract::Coronary heart disease (CHD) is the leading cause of death worldwide. Mitochondrial genetic determinant for the development of CHD remains poorly explored. We report there the clinical, genetic, molecular and biochemical characterization of a four-generation Chinese family with maternally inherited CHD. Thirteen of 32...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt256
更新日期:2013-10-15 00:00:00
abstract::Facio-scapulo-humeral dystrophy (FSHD) results from deletions in the subtelomeric macrosatellite D4Z4 array on the 4q35 region. Upregulation of the DUX4 retrogene from the last D4Z4 repeated unit is thought to underlie FSHD pathophysiology. However, no one knows what triggers muscle defect and when alteration arises. ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt272
更新日期:2013-10-15 00:00:00
abstract::Huntington disease is caused by the expansion of a CAG repeat encoding an extended glutamine tract in a protein called huntingtin. Here, we provide evidence supporting the hypothesis that somatic increases of mutation length play a role in the progressive nature and cell-selective aspects of HD pathogenesis. Results f...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm054
更新日期:2007-05-15 00:00:00
abstract::Reduced activity of beta4-galactosyltransferase 7 (beta4GalT-7), an enzyme involved in synthesizing the glycosaminoglycan linkage region of proteoglycans, is associated with the progeroid form of Ehlers-Danlos syndrome (EDS). In the invertebrates Drosophila melanogaster and Caenorhabditis elegans, mutations in beta4Ga...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm372
更新日期:2008-04-01 00:00:00
abstract::The zinc metalloprotease ZMPSTE24 plays a critical role in nuclear lamin biology by cleaving the prenylated and carboxylmethylated 15-amino acid tail from the C-terminus of prelamin A to yield mature lamin A. A defect in this proteolytic event, caused by a mutation in the lamin A gene (LMNA) that eliminates the ZMPSTE...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds233
更新日期:2012-09-15 00:00:00
abstract::Lysosomal storage diseases are due to inherited deficiencies in various enzymes involved in basic metabolic processes. As with other genetic diseases, accurate structure data for these enzymatic proteins should help in better understanding the molecular effects of mutations identified in patients with the correspondin...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/9.6.967
更新日期:2000-04-12 00:00:00
abstract::An unresolved issue about many neurodegenerative diseases is why neurons are particularly sensitive to defects in ubiquitous cellular processes. One example is Niemann Pick type C1, caused by defects in cholesterol trafficking in all cells, but where neurons are preferentially damaged. Understanding this selective fai...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds090
更新日期:2012-06-15 00:00:00
abstract::Beside the well-known polyglutamine expansions involved in several neurodegenerative disorders, convergent recent findings pointed to the expansion of polyalanine stretches as a disease mechanism in congenital malformations, skeletal dysplasia and nervous system anomalies. Polyalanine stretches have been predicted in ...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddh251
更新日期:2004-10-01 00:00:00
abstract::Loss-of-function mutations of the X-chromosome gene UPF3B cause male neurodevelopmental disorders (NDDs) via largely unknown mechanisms. We investigated initially by interrogating a novel synonymous UPF3B variant in a male with absent speech. In silico and functional studies using cell lines derived from this individu...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa151
更新日期:2020-08-29 00:00:00
abstract::Parkinson disease (PD) is the second most common neurodegenerative disorder. We studied 754 affected individuals, comprising 425 sibling pairs, to identify PD susceptibility genes. Screening of the parkin gene was performed in a subset of the sample having earlier age of PD onset or a positive LOD score with a marker ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg270
更新日期:2003-10-15 00:00:00
abstract::Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder affecting carriers of the fragile X-premutation, who have an expanded CGG repeat in the 5'-UTR of the FMR1 gene. FXTAS is characterized by progressive development of intention tremor, ataxia, parkinsonism and neuropsychologi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv216
更新日期:2015-09-01 00:00:00
abstract::Current evidence indicates that excess brain cholesterol regulates amyloid-β (Aβ) deposition, which in turn can regulate cholesterol homeostasis. Moreover, Aβ neurotoxicity is potentiated, in part, by mitochondrial glutathione (mGSH) depletion. To better understand the relationship between alterations in cholesterol h...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt201
更新日期:2013-09-01 00:00:00
abstract::What would define real progress in the field of deafness research in fundamental and medical terms? In fundamental terms, progress would be measured by an improvement in our knowledge of the development and physiology of the ear. In medical terms, progress would lead to the division of the broad category of hearing de...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/7.10.1589
更新日期:1998-01-01 00:00:00
abstract::Progressive forms of multiple sclerosis lead to chronic disability, substantial decline in quality of life and reduced longevity. It is often suggested that they occur independently of inflammation. Here we investigated the disease progression in mouse models carrying PLP1 point mutations previously found in patients ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw296
更新日期:2016-11-01 00:00:00
abstract::Cellular protein homeostasis is achieved by a delicate network of molecular chaperones and various proteolytic processes such as ubiquitin-proteasome system (UPS) to avoid a build-up of misfolded protein aggregates. The latter is a common denominator of neurodegeneration. Neurons are found to be particularly vulnerabl...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv445
更新日期:2016-01-15 00:00:00
abstract::l-2-Hydroxyglutaric aciduria (l-2-HGA) is characterized by progressive deterioration of central nervous system function including epilepsy and macrocephaly in 50% of cases, and elevated levels of l-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid (CSF). Nuclear magnetic resonance imaging shows distinct a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh300
更新日期:2004-11-15 00:00:00
abstract::Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant disease caused by mutations in the gene encoding protein kinase C gamma (PKC gamma). We report an SCA14 family with a novel deletion of a termination-codon-containing region, resulting in a missense change and a C-terminal 13-amino-acid extension with inc...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp298
更新日期:2009-10-01 00:00:00
abstract::Glycosylation with O-linked β-N-acetylglucosamine (O-GlcNAc) is one of the protein glycosylations affecting various intracellular events. However, the role of O-GlcNAcylation in neurodegenerative diseases such as Alzheimer's disease (AD) is poorly understood. Mitochondrial adenosine 5'-triphosphate (ATP) synthase is a...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv358
更新日期:2015-11-15 00:00:00
abstract::Intronic expansion of a hexanucleotide GGGGCC repeat in the chromosome 9 open reading frame 72 (C9ORF72) gene is the major cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. However, the cellular function of the C9ORF72 protein remains unknown. Here, we demonstrate that C9ORF72 regulate...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu068
更新日期:2014-07-01 00:00:00
abstract::X-linked spinal and bulbar muscular atrophy (SBMA; Kennedy's disease) is a polyglutamine (polyQ) disease in which the affected males suffer progressive motor neuron degeneration accompanied by signs of androgen insensitivity, such as gynecomastia and reduced fertility. SBMA is caused by CAG repeat expansions in the an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl148
更新日期:2006-07-15 00:00:00
abstract::Ankylosing spondylitis (AS) remains difficult to diagnose before irreversible damage to sacroiliac joint is noticeable. Circulating microRNAs have demonstrated to serve as diagnostic tools for several human diseases. Here, we analysed plasma microRNAs to identify potential AS biomarkers. Higher expression levels of mi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy008
更新日期:2018-03-01 00:00:00
abstract::Oxidative stress is a prominent feature of Huntington disease (HD), and we have shown previously that reduced levels of hace1 (HECT domain and Ankyrin repeat containing E3 ubiquitin protein ligase 1) in patient striatum may contribute to the pathogenesis of HD. Hace1 promotes the stability of Nrf2 and thus plays an im...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx394
更新日期:2018-01-15 00:00:00
abstract::Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroids, pancreas and anterior pituitary that represents one of the familial cancer syndromes. The MEN1 locus has been previously localised to chromosome 11q13, and a <300 kb gene-rich region flanked centr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.7.1177
更新日期:1997-07-01 00:00:00
abstract::Eukaryotic elongation factor 1A (EEF1A), is encoded by two distinct isoforms, EEF1A1 and EEF1A2; whereas EEF1A1 is expressed almost ubiquitously, EEF1A2 expression is limited such that it is only detectable in skeletal muscle, heart, brain and spinal cord. Currently, the role of EEF1A2 in normal cardiac development an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx239
更新日期:2017-09-15 00:00:00
abstract::Huntington disease is caused by the expansion of a CAG repeat encoding an extended glutamine tract in a protein called huntingtin. Although the mutant protein is widely expressed, the earliest and most striking neuropathological changes are observed in the striatum. Here we show dramatic mutation length increases (gai...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg352
更新日期:2003-12-15 00:00:00
abstract::Prolactinomas are the most frequent type of pituitary tumors, which represent 10-20% of all intracranial neoplasms in humans. Prolactinomas develop in mice lacking the prolactin receptor (PRLR), which is a member of the cytokine receptor superfamily that signals via Janus kinase-2-signal transducer and activator of tr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddy396
更新日期:2019-03-15 00:00:00