Abstract：
:Haploinsufficiency for the HMG-box transcription factor SOX2 results in abnormalities of the human ventral forebrain and its derivative structures. These defects include anophthalmia (absence of eye), microphthalmia (small eye) and hypothalamic hamartoma (HH), an overgrowth of the ventral hypothalamus. To determine how Sox2 deficiency affects the morphogenesis of the ventral diencephalon and eye, we generated a Sox2 allelic series (Sox2(IR), Sox2(LP), and Sox2(EGFP)), allowing for the generation of mice that express germline hypomorphic levels (<40%) of SOX2 protein and that faithfully recapitulate SOX2 haploinsufficient human phenotypes. We find that Sox2 hypomorphism significantly disrupts the development of the posterior hypothalamus, resulting in an ectopic protuberance of the prechordal floor, an upregulation of Shh signaling, and abnormal hypothalamic patterning. In the anterior diencephalon, both the optic stalks and optic cups (OC) of Sox2 hypomorphic (Sox2(HYP)) embryos are malformed. Furthermore, Sox2(HYP) eyes exhibit a loss of neural potential and coloboma, a common phenotype in SOX2 haploinsufficient humans that has not been described in a mouse model of SOX2 deficiency. These results establish for the first time that germline Sox2 hypomorphism disrupts the morphogenesis and patterning of the hypothalamus, optic stalk, and the early OC, establishing a model of the development of the abnormalities that are observed in SOX2 haploinsufficient humans.
journal_name
Mech Devjournal_title
Mechanisms of developmentauthors
Langer L,Taranova O,Sulik K,Pevny Ldoi
10.1016/j.mod.2012.04.001subject
Has Abstractpub_date
2012-03-01 00:00:00pages
1-12issue
1-4eissn
0925-4773issn
1872-6356pii
S0925-4773(12)00026-3journal_volume
129pub_type
杂志文章abstract：:Polycomb group (PcG) proteins regulate and maintain expression pattern of genes set early during development. Although originally isolated as regulators of homeotic genes, PcG members play a key role in epigenetic mechanisms that maintain the expression state of a large number of genes. All members of the two polycomb...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/j.mod.2015.07.013
更新日期：2015-11-01 00:00:00
abstract：:Endothelial to mesenchymal transition (EMT) that occurs during cardiac outflow tract (OFT) development is critical for formation of the semilunar valves. Fibulin-1 (Fbln1) is an extracellular matrix protein that is present at several sites of EMT, including the OFT (i.e., E9.5-10.5). The aim of this study was to deter...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/j.mod.2014.12.005
更新日期：2015-05-01 00:00:00
abstract：:The homeotic gene abdominal-A (abd-A) is normally expressed in parasegments 7 to 13. We find that the initial distribution of the product is approximately uniform within this domain, but the subsequent elaboration of the expression pattern results in differences between, as well as within, parasegments. We have invest...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/0925-4773(94)90034-5
更新日期：1994-04-01 00:00:00
abstract：:Blood vessel maturation, which is characterized by the investment of vascular smooth muscle cells (vSMCs) around developing blood vessels, begins when vessels remodel into a hierarchy of proximal arteries and proximal veins that branch into smaller distal capillaries. The ultimate result of maturation is formation of ...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/j.mod.2019.02.002
更新日期：2019-04-01 00:00:00
abstract：:We have characterised the transdifferentiation of human HepG2 (hepatoma) cells to pancreatic cells following introduction of an activated version of the pancreatic transcription factor Pdx1 (XlHbox8-VP16). The following questions are addressed: (1) are all types of pancreatic cells produced? (2) is the requirement for...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/j.mod.2005.01.001
更新日期：2005-06-01 00:00:00
abstract：:The embryonic fins and the tip of adult fins of teleost fish are supported by rows of straight, unmineralized fibrils called actinotrichia. The proximal ends of the actinotrichia are bundled and the mineralized bones called lepidotrichia are made along them. Since malformation in actinotrichia causes wavy fin bones, t...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/j.mod.2018.08.010
更新日期：2018-10-01 00:00:00
abstract：:Basic helix-loop-helix (bHLH) proteins of the Achaete/Scute (Ac/Sc) family are required for neurogenesis in both Drosophila and vertebrates. These transcription factors are commonly referred to as 'proneural' factors, as they promote neural fate in many contexts. Although Ac/Sc proteins have been studied in Hydra, jel...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/j.mod.2008.06.002
更新日期：2008-09-01 00:00:00
abstract：:Six genes are vertebrate homologues of the homeobox-containing gene sine oculis, which plays an essential role in controlling Drosophila compound eye development. Here we report the identification and expression patterns of all three subfamilies of Xenopus Six genes. Two Six2 subfamily genes (Six1, Six2) showed very s...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/s0925-4773(00)00572-4
更新日期：2001-03-01 00:00:00
abstract：:Terminal portions of the Drosophila body pattern are specified by an extracellular ligand generated at each end of the early syncytial embryo. This ligand triggers the localized transcription of two gap segmentation genes, tailles (tll) and huckebein (hkb) through a signal transduction cascade involving the receptor t...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/0925-4773(94)90006-x
更新日期：1994-10-01 00:00:00
abstract：:It is now well established that apoptosis is induced in response to mechanical strain. Indeed, increasing compressive forces induces apoptosis in confined spheroids of tumour cells, whereas releasing stress reduces apoptosis in spheroids cultivated in free suspension (Cheng et al., 2009). Apoptosis can also be induced...
journal_title：Mechanisms of development
pub_type： 杂志文章,评审
doi：10.1016/j.mod.2016.10.001
更新日期：2017-04-01 00:00:00
abstract：:The recent determination and annotation of the entire euchromatic sequence of the Drosophila melanogaster genome predicted the existence of about 13600 different genes (Science 287 (2000) 2185; http://www.fruitfly.org/annot/index.html). In parallel, the Berkeley Drosophila Genome Project (BDGP) has undertaken systemat...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/s0925-4773(01)00566-4
更新日期：2002-01-01 00:00:00
abstract：:To analyse the possible roles of Drosophila tumour suppressor genes, 1(2)gl and 1(2)gd, in differentiation programmes of imaginal cells, we investigated their interactions with two segment polarity genes, viz., cubitus interruptus Dominant (ci-D) and engrailed (en), by examining their patterns of expression in tumouro...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/0925-4773(95)00367-3
更新日期：1995-06-01 00:00:00
abstract：:Mitochondrial large rRNA (mtlrRNA) and small rRNA (mtsrRNA) have been identified as components of germinal granules in Drosophila. We have previously reported that mtlrRNA is present on the germinal granules in Xenopus embryos. Here we report that mtsrRNA is also a common component of the germinal granules. Extra-mito...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/s0925-4773(00)00553-0
更新日期：2001-03-01 00:00:00
abstract：:The vertebrate neural tube develops by two distinct mechanisms. Anteriorly, in the brain and future trunk (cervicothoracic) region, 'primary neurulation' occurs, where an epithelial sheet rolls or bends into a tube. Posteriorly, in the future lumbar and tail region, the neural tube forms by 'secondary neurulation', wh...
journal_title：Mechanisms of development
pub_type： 杂志文章,评审
doi：10.1016/j.mod.2004.04.022
更新日期：2004-10-01 00:00:00
abstract：:Hox gene expression imparts segment identity to body structures along the anterior-posterior axis and is tightly governed by higher order chromatin mechanisms. Chromatin regulatory features of the homeotic complex are best defined in Drosophila melanogaster, where multiple cis-regulatory elements have been identified ...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/j.mod.2015.07.015
更新日期：2015-11-01 00:00:00
abstract：:Drosophila Spitz is a homolog of transforming growth factor alpha (TGF-alpha) and is an activating ligand for the EGF receptor (Egfr). It has been shown that Star is required for Spitz activity. Here we show that Star is quantitatively limiting for Spitz production during eye development. We also show that Star and Sp...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/s0925-4773(01)00432-4
更新日期：2001-09-01 00:00:00
abstract：:XLPOU3 is a member of the Xenopus POU domain family of genes, encoding a class of homeodomain-containing transcription factors implicated in cell differentiation during development. Here we describe the isolation and characterisation of XLPOU3b, an allelic genomic counterpart of the XLPOU3 cDNA previously described (B...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/s0925-4773(96)00563-1
更新日期：1996-08-01 00:00:00
abstract：:Each sensory organ of the Drosophila peripheral nervous system is derived from a single sensory organ precursor cell (SOP). These originate in territories defined by expression of the proneural genes of the Achaete-Scute complex (AS-C). Formation of ectopic sensilla outside these regions is prevented by transcriptiona...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/s0925-4773(02)00183-1
更新日期：2002-09-01 00:00:00
abstract：:Nuclear translocation, driven by the motility apparatus consisting of the cytoplasmic dynein motor and microtubules, is essential for cell migration during embryonic development. Bicaudal-D (Bic-D), an evolutionarily conserved dynein-interacting protein, is required for developmental control of nuclear migration in Dr...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/j.mod.2004.08.005
更新日期：2005-01-01 00:00:00
abstract：:Nemo-like kinases define a novel family of serine/threonine kinases that are involved in integrating multiple signaling pathways. They are conserved regulators of Wnt/Wingless pathways, which may coordinate Wnt with TGFbeta-mediated signaling. Drosophila nemo was identified through its involvement in epithelial planar...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/s0925-4773(02)00289-7
更新日期：2002-11-01 00:00:00
abstract：:T-box genes constitute a conserved multi-gene family with important roles in many developmental processes. In this report, we describe the cloning and expression analysis of a novel mouse T-box gene, Tbx20. Expression is prominent in the extraembryonic mesoderm, in the developing heart, the eye anlage and motor neuron...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/s0925-4773(00)00499-8
更新日期：2001-01-01 00:00:00
abstract：:Cloning and sequencing of mouse Mf2 (mesoderm/mesenchyme forkhead 2) cDNAs revealed an open reading frame encoding a putative protein of 492 amino acids which, after in vitro translation, binds to a DNA consensus sequence. Mf2 is expressed at high levels in the ventral region of newly formed somites, in sclerotomal de...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/s0925-4773(97)00157-3
更新日期：1998-01-01 00:00:00
abstract：:Active repression of gene expression mediated by unliganded nuclear receptors plays crucial roles in early development of vertebrates. N-CoR (nuclear receptor co-repressor) is the first identified co-repressor that can repress retinoic acid (RA) inducible gene transcription in the absence of RA. Previously, N-CoR was ...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/j.mod.2009.09.001
更新日期：2009-10-01 00:00:00
abstract：:The normal embryogenesis of marine animals is typically confined to a species-specific range of temperatures. Within that temperature range development results in a consistent, or canalized, phenotype, whereas above and below the range abnormal phenotypes are produced. This study reveals a high temperature threshold, ...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/j.mod.2019.04.002
更新日期：2019-06-01 00:00:00
abstract：:We describe the cloning, expression pattern and functional overexpression analysis of Xotx5b, a new member of the Otx gene family in Xenopus laevis. Early expression of Xotx5b resembles that of Xotx2, being detected in the organizer region at early gastrula stage, and, shortly after, also in anterior neuroectoderm. Du...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/s0925-4773(00)00367-1
更新日期：2000-08-01 00:00:00
abstract：:The diencephalon is the caudal part of the developing forebrain that gives rise to the epithalamus, thalamus, hypothalamus and retina. The mature diencephalon is functionally and anatomically parceled into well-defined nuclei. In an effort to understand how this region of the brain develops we examined the expression ...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/s0925-4773(02)00091-6
更新日期：2002-07-01 00:00:00
abstract：:During early vertebrate development, a series of neuromeres divides the central nervous system from the forebrain to the spinal cord. Here we examine in more detail the expression of Wnt-3, a member of the Wnt gene family of secreted proteins, in the developing diencephalon, in comparison to the expression of the home...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/0925-4773(92)90042-i
更新日期：1992-12-01 00:00:00
abstract：:In order to analyze the expression pattern of the 5'-nucleotidase (5nt) gene in Dictyostelium, we made a fusion construct in which the 5nt promoter directed the expression of beta-galactosidase gene. The reporter gene was not active in vegetative amoebae but was expressed during the aggregation stage. At the slug stag...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/s0925-4773(01)00580-9
更新日期：2002-01-01 00:00:00
abstract：:Hair cell (HC) and supporting cell (SC) productions are completed during early embryonic development of the mammalian cochlea. This study shows that acutely dissociated cells from the newborn rat organ of Corti, developed into so-called otospheres consisting of 98% nestin (+) cells when plated on a non-adherent substr...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/s0925-4773(01)00642-6
更新日期：2002-03-01 00:00:00
abstract：:In Xenopus and zebrafish, BMP2, 4 and 7 have been implicated, after the onset of zygotic expression, in inducing and maintaining ventro-lateral cell fate during early development. We provide evidence here that a maternally expressed bone morphogenetic protein (BMP), Radar, may control early ventral specification in ze...
journal_title：Mechanisms of development
pub_type： 杂志文章
doi：10.1016/s0925-4773(00)00470-6
更新日期：2000-12-01 00:00:00
