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At least 811 records · Page 45Linked to original sources
PubMed2000

Correlation between gene functions and developmental expression patterns in the mouse cerebellum.

Quantitative changes of 419 gene transcripts during postnatal mouse cerebellar development were accurately determined with a novel polymerase chain reaction (PCR)-based technique. About 70% of the genes showed differences in expression levels, and the magnitude of difference was relatively small. By hierarchic cluster analysis of developmental expression patterns, the genes were categorized into 19 clusters, which were subsequently assembled into four major groups: group 1, with elevation of gene expression throughout the time course; group 2, with relatively unchanged levels; group 3, with transiently high expression at approximately 12 days; and group 4, with highest expression at approximately 4 days. Genes related to brain functions were segregated into several clusters of group 1 and group 3: the same clusters in which cerebellum-specific genes were also segregated. Genes for protein synthesis belonged to group 4. Genes with housekeeping functions belonged to group 2. Western blotting analysis of representative protein products of each group revealed correlation with the mRNA level for those belonging to group 1 and group 4, but not necessarily in the other groups. The close correlation of algorithmically categorized temporal expression patterns of genes with their functions will be useful for estimating the functions of thousands of novel genes.

Animals↗
PubMed2004

Gene amplification as a developmental strategy: isolation of two developmental amplicons in Drosophila.

Gene amplification is known to be critical for upregulating gene expression in a few cases, but the extent to which amplification is utilized in the development of diverse organisms remains unknown. By quantifying genomic DNA hybridization to microarrays to assay gene copy number, we identified two additional developmental amplicons in the follicle cells of the Drosophila ovary. Both amplicons contain genes which, following their amplification, are expressed in the follicle cells, and the expression of three of these genes becomes restricted to specialized follicle cells late in differentiation. Genetic analysis establishes that at least one of these genes, yellow-g, is critical for follicle cell function, because mutations in yellow-g disrupt eggshell integrity. Thus, during follicle cell differentiation the entire genome is overreplicated as the cells become polyploid, and subsequently specific genomic intervals are overreplicated to facilitate gene expression.

Animals↗
PubMed2003

Expression of foreign genes in lamprey embryos: an approach to study evolutionary changes in gene regulation.

Evolution in development can be viewed as a sequence of changes in gene regulation. To investigate the cross-species compatibility of 5' upstream regulatory regions, we introduced exogenous gene constructs derived from a gnathostome genome into fertilized eggs of the Japanese lamprey, Lampetra japonica, a sister group of the gnathostomes. Eggs were injected with gene constructs in which a sequence encoding the green fluorescent protein (GFP) had been located downstream of either a virus promoter or 5' regulatory regions of medaka actin genes. Reporter gene expression was recorded for more than a month starting two days after injection. Although the expression patterns were highly mosaic and differed among individuals, GFP was expressed predominantly in the striated muscles of lamprey embryos when driven by the 5' upstream regions of the medaka muscle actin genes. This implies that a pan-vertebrate muscle-specific gene regulatory mechanism may have evolved before the agnathan/gnathostome divergence. This gene-transfer technique potentially facilitates the visualization of cells in various differentiating tissues throughout development. The introduction of developmental genes of the lamprey or other animals into lamprey embryos is another potentially important application, one that could provide us with information on the evolutionary changes in functions of genes or gene cascades.

Actins↗
PubMedDate not supplied

Gene transfer and expression studies in cultured avian neural crest cells differentiating into melanocytes.

Neural crest cells obtained from explanted neural tubes take up, express, and retain exogenous DNA applied by the CaPO4 co-precipitation method during their differentiation into melanocytes. High efficiencies of gene transfer were obtained with both supercoiled DNA and intact phage particles; linear DNA or DNA from the phage yielded very low efficiencies. There is some evidence that transferred gene expression is differentiation dependent. The system should be useful for studies concerned with the analysis of cell developmental genes and their regulatory elements.

Animals↗
PubMed1996

[Molecular biological aspects of brush border membrane hydrolases and brush border membrane].

This article is a review of the current understanding of molecular mechanisms in the regulation of brush border membrane (BBM) hydrolase expression. The promoters of BBM hydrolase genes have a number of binding sites for nuclear transcription factors which may regulate the tissue specific and developmental gene expression. The rate limiting step of BBM hydrolase expression is the posttranslational processing and intracellular transport of the hydrolases. The informations for apical sorting of BBM hydrolases may present in the ectodomain of molecule, while the basolateral sorting signal has been reported to be localized in the cytosolic domain. The disturbance of transcription or posttranslational processing may result in abnormal expression of the particular hydrolase which is clinically identified as a BBM disease.

Biological Transport↗
PubMed2005

PldB, a putative phospholipase D homologue in Dictyostelium discoideum mediates quorum sensing during development.

Quorum sensing, also known as cell-density sensing in the unicellular eukaryote Dictyostelium discoideum, is required for efficient entry into the differentiation and development segment of its life cycle. Quorum sensing is accomplished by simultaneously secreting and sensing the glycoprotein Conditioned Medium Factor, or CMF. When the density of starving cells is high, CMF levels are high, which leads to aggregation followed by development. Here, we describe the role of pldB, a gene coding for a putative phospholipase D (PLD) homologue, in quorum sensing. We find that in submerged culture, adding butanol, an inhibitor of PLD-catalyzed phosphatidic acid production, allows cells to bypass the requirement for CMF mediated quorum sensing and aggregate at low cell density. Deletion of pldB mimics the presence of butanol, allowing cells to aggregate at low cell density. pldB- cells also initiate and finish aggregation rapidly. Analysis of early developmental gene expression in pldB- cells reveals that the cyclic AMP receptor cAR1 is expressed at higher levels earlier than in wild-type cells, which could explain the rapid aggregation phenotype. As would be predicted, cells overexpressing pldB are unable to aggregate even at high cell density. Adding CMF to these pldB- overexpressing cells does not rescue aggregation. Both of these phenotypes are cell autonomous, as mixing a small number of pldB- cells with wild-type cells does not cause the wild-type cells to behave like pldB- cells.

Amino Acid Sequence↗
PubMed2003

How clinicians add to knowledge of development.

Studies of human birth defects and developmental disorders have made major contributions to our understanding of development. Rare human syndromes have allowed identification of important developmental genes, and revealed mechanisms such as uniparental disomy and unstable trinucleotide repeats that were not suspected from animal studies. Some aspects of development, in particular cognitive development, can only be studied in human beings. Basic developmental mechanisms are very highly conserved across a very wide range of animals, making for a rich interplay between animal and human studies. Often, clinical studies identify a gene, or suggest a hypothesis, that can then be investigated in animals.

Animals↗
PubMed2005

Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals.

In the mammalian auditory system, sensory cell loss resulting from aging, ototoxic drugs, infections, overstimulation and other causes is irreversible and leads to permanent sensorineural hearing loss. To restore hearing, it is necessary to generate new functional hair cells. One potential way to regenerate hair cells is to induce a phenotypic transdifferentiation of nonsensory cells that remain in the deaf cochlea. Here we report that Atoh1, a gene also known as Math1 encoding a basic helix-loop-helix transcription factor and key regulator of hair cell development, induces regeneration of hair cells and substantially improves hearing thresholds in the mature deaf inner ear after delivery to nonsensory cells through adenovectors. This is the first demonstration of cellular and functional repair in the organ of Corti of a mature deaf mammal. The data suggest a new therapeutic approach based on expressing crucial developmental genes for cellular and functional restoration in the damaged auditory epithelium and other sensory systems.

Adenoviridae↗
PubMed1990

A pleiotropic defect in cAMP-regulated gene expression in the Dictyostelium agg- mutant synag 7.

During differentiation of Dictyostelium discoideum, cAMP functions as a diffusible, extracellular signal to direct chemotaxis and regulate developmental gene expression. The availability of signal-transduction mutants of Dictyostelium now makes it feasible to pursue a genetic analysis of cAMP signaling. The synag 7 mutant is defective in receptor-mediated adenylate cyclase stimulation and cannot relay a cAMP signal. To further characterize this mutant, mRNA levels of several cAMP-regulated genes were measured during development. cAMP-regulated gene expression was found to be dramatically altered in synag 7:several different genes which require cAMP for expression in wild-type cells were induced in synag 7 in the absence of cAMP. In addition, the gene-encoding discoidin I, which is normally expressed in starved cells and repressed by cAMP, is expressed at very low levels in starved synag 7 cells, possibly due to precocious repression. These results suggest that a pleiotropic regulator of cAMP-regulated gene expression is uncoupled from its normal controls during development in synag 7.

Actins↗
PubMed1998

Regulation of the expression of a gene encoding beta-endoglucanase secreted by Myxococcus xanthus during growth: role of genes involved in developmental regulation.

An endoglucanase, CelA, is secreted by Myxococcus xanthus only during exponential growth. The production of this enzyme is decreased by mutations in 5 different genes (Exc +/- phenotype), three of which correspond to asg genes which regulate the production of an early cell-to-cell signal in development. Transcription of celA is decreased in two of these Exc +/- mutants, whereas a post-transcriptional step is affected in two other Exc- mutants. Thus, asg genes, in addition to regulating the onset of development, also regulate a gene (celA) that is expressed during exponential growth and that is not involved in development.

Amino Acid Sequence↗
PubMed2002

Different regulation of T-box genes Tbx4 and Tbx5 during limb development and limb regeneration.

The T-domain transcription factors Tbx4 and Tbx5 have been implicated, by virtue of their limb-type specific expression, in controlling the identity of vertebrate legs and arms, respectively. To study the roles of these genes in developing and regenerating limbs, we cloned Tbx4 and Tbx5 cDNAs from the newt, and generated antisera that recognize Tbx4 or Tbx5 proteins. We show here that, in two urodele amphibians, newts and axolotls, the regulation of Tbx4 and Tbx5 differs from higher vertebrates. At the mRNA and protein level, both Tbx4 and Tbx5 are expressed in developing hindlimbs as well as in developing forelimbs. The coexpression of these genes argues that additional factors are involved in the control of limb type-specific patterns. In addition, newt and axolotl Tbx4 and Tbx5 expression is regulated differently during embryogenesis and regenerative morphogenesis. During regeneration, Tbx5 is exclusively upregulated in the forelimbs, whereas Tbx4 is exclusively upregulated in the hindlimbs. This indicates that, on a molecular level, different regulatory mechanisms control the shaping of identical limb structures and that regeneration is not simply a reiteration of developmental gene programs.

Ambystoma mexicanum↗
PubMed2001

A homeotic mutation in the trithorax SET domain impedes histone binding.

Trithorax (TRX) is a Drosophila SET domain protein that is required for the correct expression of homeotic genes. Here, we show that the TRX SET domain efficiently binds to core histones and nucleosomes. The primary target for the SET domain is histone H3 and binding requires the N-terminal histone tails. The previously described trx(Z11) mutation changes a strictly conserved glycine in the SET domain to serine and causes homeotic transformations in the fly. We found that this mutation selectively interferes with histone binding, suggesting that histones represent a critical target during developmental gene regulation by TRX.

Animals↗
PubMed2004

Acceleration of early chick embryo morphogenesis by insulin is associated with altered expression of embryonic genes.

In the present study, we show that insulin accelerates early morphogenesis in gastrulating chick embryo explants cultured in vitro, whereas antiserum to insulin adversely affects this process. Comparison between length of body axis of control and treated embryos clearly brings out the significant acceleration of development by excess insulin (0.175 to 17.5 nM). In embryos treated with 87.5 and 175 nM insulin, a high occurrence of abnormalities is observed. Treatment of embryos with antiserum to porcine insulin results in a high percentage of abnormalities, particularly in the forming neural tube. In situ hybridization of whole embryos using digoxigenin-labeled riboprobes showed that insulin modifies the expression of crucial developmental genes within 2 hours. While Brachyury, a pan-mesodermal marker gene, ERNI, the earliest known marker for neural induction in chick, and noggin, important in neural tube patterning, are upregulated, expression of goosecoid, necessary for gastrulation movements, does not appear to be significantly altered. During the same time, insulin does not exert any mitogenic effect on chick embryonic cells as assessed by nuclear counts. These findings demonstrate that insulin plays an important role in the early morphogenesis of the chick embryo. The function of insulin appears to be mediated by specific genes which orchestrate pattern formation during early development.

Animals↗
PubMed1996

The frequency of homozygous deletion of a developmentally regulated Vh gene (Humhv3005) is increased in patients with chronic idiopathic thrombocytopenic purpura.

Little is known of the genetic factors that may contribute to the development of chronic idiopathic thrombocytopenic purpura (cITP). We have previously shown that a developmentally regulated Vh gene (Humhv3005) is absent in 10/41 (24%) of patients with systemic lupus erythematosus while it is absent in only 7/88 (8%) of normal controls. This finding suggests that a homozygous deletion of an Ig variable (V) gene may alter the immune system and thus predispose the host to an autoimmune disorder. We have analyzed the same gene in 44 patients with cITP and found that Humhv3005 and like genes were absent in a higher percentage of patients (14 of 44, 31.8%) than they were absent in either normals (7/88, 8%, p = 0.002) or thrombocytopenic patients without cITP (6/53, 11.3%, p = 0.042); the hv3005 deletion frequency in the latter group did not differ from that in normals (P = 0.74). These data suggest that deletions of Humhv3005 and/or highly homologous Vh genes may predispose individuals to the development of cITP, and may contribute toward production of pathogenic antiplatelet antibodies.

Chronic Disease↗
PubMed2006

Long-range upstream and downstream enhancers control distinct subsets of the complex spatiotemporal Sox9 expression pattern.

SOX9 is an evolutionary conserved transcription factor that is expressed in a variety of tissues, with essential functions in cartilage, testis, heart, glial cell, inner ear and neural crest development. By comparing human and pufferfish genomic sequences, we previously identified eight highly conserved sequence elements between 290 kb 5' and 450 kb 3' to human SOX9. In this study, we assayed the regulatory potential of elements E1 to E7 in transgenic mice using a lacZ reporter gene driven by a 529 bp minimal mouse Sox9 promoter. We found that three of these elements and the Sox9 promoter control distinct subsets of the tissue-specific expression pattern of Sox9. E3, located 251 kb 5' to SOX9, directs lacZ expression to cranial neural crest cells and to the inner ear. E1 is located 28 kb 5' to SOX9 and controls expression in the node, notochord, gut, bronchial epithelium and pancreas. Transgene expression in the neuroectoderm is mediated by E7, located 95 kb 3' to SOX9, which regulates expression in the telencephalon and midbrain, and by the Sox9 minimal promoter which controls expression in the ventral spinal cord and hindbrain. We show that E3-directed reporter gene expression in neural crest cells of the first but not of the second and third pharyngeal arch is dependent on beta-catenin, revealing a complex regulation of Sox9 in cranial neural crest cells. Moreover, we identify and discuss highly conserved transcription factor binding sites within enhancer E3 that are in good agreement with current models for neural crest and inner ear development. Finally, we identify enhancer E1 as a cis-regulatory element conserved between vertebrates and invertebrates, indicating that some cis-regulatory sequences that control developmental genes in vertebrates might be phylogenetically ancient.

Animals↗
PubMed1995

XIST expression is repressed when X inactivation is reversed in human placental cells: a model for study of XIST regulation.

Considerable evidence suggests that the X inactive transcript gene, XIST/Xist, has a role in the initial steps of X chromosome inactivation in the female mammalian embryo. It is transcribed exclusively from inactive X chromosomes, and its noncoding transcript seems to be essential for cis inactivation. Unexpected for a developmental gene, XIST continues to be expressed in adult somatic cells. To determine the effect of reversal of inactivation on the expression of XIST, we studied human X chromosomes that had been induced to reverse X inactivation by hybridization of chorionic villi cells from term placentas with mouse A9 cells. In nine hybrids with a reactivated X chromosome, XIST was either not expressed or expressed much less than the locus on the inactive X chromosome in the chorionic villi cells from which they were derived. The repressibility of XIST by reversal of inactivation in these placental cells mirrors events that occur during the ontogeny of oocytes and indicates that the locus is subject to regulation in somatic cells long after inactivation is established in the embryo. The small residual XIST activity from these active chromosomes suggests that low levels of XIST expression do not interfere with chromosome activity and raises the possibility that the induction of cis inactivation requires a certain level of XIST transcription. The chorionic villi hybrids provide an experimental system to study the developmental regulation of XIST.

Base Sequence↗
PubMed1988

A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype.

Multiple related cis-active elements required for cell-specific activation of the rat prolactin gene appear to bind a pituitary-specific positive transcription factor(s), referred to as Pit-1. DNA complementary to Pit-1 mRNA, cloned on the basis of specific binding to AT-rich cell-specific elements in the rat prolactin and growth hormone genes, encodes a 33 kd protein with significant similarity at its carboxyl terminus to the homeodomains encoded by Drosophila developmental genes. Pit-1 mRNA is expressed exclusively in the anterior pituitary gland in both somatotroph and lactotroph cell types, which produce growth hormone and prolactin, respectively. Pit-1 expression in heterologous cells (HeLa) selectively activates prolactin and growth hormone fusion gene expression, suggesting that Pit-1 is sufficient to confer a characteristic pituitary phenotype. The structure of Pit-1 and its recognition elements suggests that metazoan tissue phenotype is controlled by a family of transcription factors that bind to related cis-active elements and contain several highly conserved domains.

Amino Acid Sequence↗
PubMed2006

Adult neurogenesis and schizophrenia: a window on abnormal early brain development?

Adult neurogenesis is one of the most rapidly growing areas in neuroscience research and there is great interest in its potential role in the pathophysiology of psychiatric illness. In parallel with early development, adult neurogenesis occurs through the proliferation of precursor cells which migrate to specific regions and differentiate into neurons with characteristics indistinguishable from existing mature neurons. These findings have led to the re-definition of the concept of network plasticity in the adult brain, to include the formation of new neurons as well as new connections. This review examines the idea that adult neurogenesis may be disturbed in schizophrenia. We discuss evidence for abnormal mechanisms of neurogenesis and expression of developmental genes in schizophrenia, the influence of antipsychotic drugs on neurogenesis and the role of candidate schizophrenia susceptibility genes in adult neurogenesis. The recent discovery of molecular markers transiently expressed in newborn neurons within adult neurogenic brain regions could be used to probe whether neurogenesis is disturbed in schizophrenia. Adult neurogenesis could also be used as a unique tool for investigating genes involved in early brain development using post-mortem brains. This is particularly relevant for brain disorders with developmental origins such as schizophrenia.

Adult↗