SEARCH · PubMed Health

Results for “Genes, Developmental”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources

PubMed1997

The intranuclear organization of normal, hemizygous and excision-deficient rRNA genes during developmental amplification in Tetrahymena thermophila.

In the ciliated protozoan, Tetrahymena thermophila, the diploid germinal micronucleus contains two allelic copies of the gene for ribosomal RNA (rDNA). During genesis of new somatic macronuclei the germline rDNA gene is excised by developmentally programmed chromosome breakage and preferentially amplified to approximately 9, 000 copies. We have studied this process by fluorescence in situ hybridization. We find that initially rDNA amplification is restricted to two separate and highly confined regions of the nucleus. Analysis of nuclei that are hemizygous for the rDNA locus reveals that each focus of hybridization is derived from a single allele of the rDNA. As rDNA amplification progresses these two foci of hybridization disperse and spread throughout the macronucleus, eventually forming approximately 100-500 new nucleoli. These events are correlated with morphologically distinct developmental stages. We investigated the amplification of the C3 allele of the rDNA that confers a replication advantage over the B allele during vegetative propagation, and find no evidence for preferential amplification of the C3 early in rDNA maturation. We also show that the rmm 11 rDNA mutant allele, which is defective for developmentally programmed rDNA excision, can be amplified during the two-foci stage in mutant homozygotes and heterozygotes, but fails to amplify further and disperse into multiple nucleoli. These data indicate that amplification of the rmm 11 allele is not delayed during the initial rounds of amplification, and suggest that efficient excision is not required for this amplification to occur. We propose that rDNA amplification is a two-step process. First, the two rDNA alleles are independently amplified, while allelic copies remain closely associated. Later, copies of the rDNA disperse and are further amplified, presumably because rDNA excision has occurred, generating fully mature rDNA minichromosomes that are able to replicate to high copy number.

Alleles↗

PubMed2004

Fine mapping of the 2p11 dyslexia locus and exclusion of TACR1 as a candidate gene.

Developmental dyslexia, or reading disability, is a multigenic complex disease for which at least five loci, i.e. DYX1-3 and DYX5-6, have been clearly identified from the human genome. To date, DYX1C1 is the only dyslexia candidate gene cloned. We have previously reported linkage to 2p11 and 7q32 in 11 Finnish pedigrees. Here, we report the fine mapping of the approximately 40-cM linked region from chromosome 2 as we increased marker density to one per 1.8 cM. Linkage was supported with the highest NPL score of 3.0 (P=0.001) for marker D2S2216. Association analysis using the six pedigrees showing linkage pointed to marker D2S286/rs3220265 (P value <0.001) in the near vicinity of D2S2216. We went on to further characterise this approximately 15-cM candidate region (D2S2110-D2S2181) by adding six SNPs covering approximately 670 kb centred at D2S286/rs3220265. A haplotype pattern could no longer be observed in this region, which was therefore excluded from the candidate area. This also excluded the TACR1 (tachykinin receptor 1) gene, located at marker D2S286. The dyslexia candidate region on 2p11 is, therefore, now limited to the chromosomal area D2S2116-D2S2181, which is approximately 12 Mbp of human sequence and is at a distinct location from the previously reported DYX3 locus, raising the possibility of two distinct loci on chromosome 2p.

Blotting, Northern↗

PubMed1984

Expression of the cardiac ventricular alpha- and beta-myosin heavy chain genes is developmentally and hormonally regulated.

The cardiac ventricular myosin phenotype is developmentally and hormonally regulated. The genes coding for the two myosin heavy chains ( MHCs ), alpha and beta, have been recently isolated and characterized. In this study, we establish the precise temporal expression of these MHC genes in correlation with the myosin phenotype both during cardiac development and in response to different thyroid hormone levels and also document their expression in other muscle tissues. The close correlation observed between the relative abundance of the alpha- and beta-MHC mRNAs and corresponding isozymes demonstrates that the MHC phenotype is produced by the expression of the alpha- and beta-MHC genes and is regulated by changes in the level of their respective mRNAs. The opposite effect of thyroid hormone on the expression of the alpha- and beta-MHC genes in the ventricular myocardium indicates that these genes are regulated in an antithetic fashion. Finally, the MHC mRNAs encoded by the alpha- and beta-MHC genes are also present in the atrial myocardium and in the soleus, respectively.

Animals↗

PubMed1997

Closely related genes encode developmental and tissue isoforms of porcine cytochrome P450 aromatase.

We examined the chromosomal basis for the synthesis of tissue (ovary, endometrium/placenta, and peri-implantation blastocyst) isoforms of cytochrome P450 aromatase in the pig. DNA fragments derived from three distinct porcine aromatase chromosomal genes were cloned and characterized. The porcine type III aromatase gene encoding the blastocyst aromatase isoform was found to consist of nine coding exons and two mutually exclusive, 5' untranslated exons (designated E1A and E1B), collectively spanning 30 kb or more. The porcine type II aromatase gene, encoding the endometrial/placental aromatase isoform, was identified by cloning of a genomic DNA fragment spanning the corresponding exons 7, 8, and 9. The DNA inserts of two other phage clones encompassed exons 2, 3, and 4 of a third chromosomal gene (type I) encoding the ovarian aromatase isoform. All intron-exon junctions in these genomic fragments were found to be identical in relative positions to those of the single-copy human aromatase gene. Comparisons of cDNA and genomic sequences indicated that nucleotide sequence variation was not uniform across the corresponding exons of these genes and that the corresponding intronic sequences were conserved. The type II and type III aromatase genes were localized to the same regional location (q16-17) on swine chromosome 1, which is homologous to the human chromosome 15 region (q21.1) in which the human aromatase gene resides. Results demonstrate that the three aromatase genes characterized in the present study appear to be similar in their overall structural organization and most likely are clustered, which could have resulted from at least two independent gene duplication events. The presence of multiple aromatase genes constitutes a newly described mechanism by which aromatase enzyme biosynthesis and functional activity can be regulated in a tissue and temporal fashion and serves to highlight further the complexity of aromatase gene expression in mammals. Moreover, the presence of a unique aromatase gene that is highly expressed in pig blastocysts may constitute a paradigm for other mammals (e.g., equids, rabbit, hamster) whose peri-implantation blastocysts are estrogenic.

Animals↗

PubMed1993

Spatial and temporal controls of the Aspergillus brlA developmental regulatory gene.

The Aspergillus nidulans brlA gene encodes a transcriptional regulator of central importance in controlling conidiophore development. I have determined the effects of mutations in other developmental regulatory genes on expression of a brlA-lacZ fusion gene. Deletion of brlA reduced beta-galactosidase levels by half and led to delocalization of enzyme accumulation. The medA26 and abaA2 developmental mutations led to overexpression of the fusion gene without altering spatial specificity. In contrast, the stuA1 mutation did not affect the timing or levels of brlA expression during induction, but instead resulted in spatial derangement of expression. These results and the phenotypes of the mutants suggest a model in which subsets of morphogenetic loci are controlled by differing levels and combinations of regulatory gene products, which are themselves determined by interactions among the regulatory genes.

Amino Acid Sequence↗

PubMed2004

Identification of differentially expressed and developmentally regulated genes in medulloblastoma using suppression subtraction hybridization.

To increase our understanding of the molecular pathogenesis of medulloblastoma (MB), we utilized the technique of suppression subtractive hybridization (SSH) to identify genes that are dysregulated in MB when compared to cerebellum. SSH-enriched cDNA libraries from both human and Ptch+/- heterozygous murine MBs were generated by subtracting common cDNAs from corresponding non-neoplastic cerebellum. For the human classic MB library, total human cerebellar RNA was used as control tissue; for the Ptch+/- heterozygous MB, non-neoplastic cerebellum from an unaffected Ptch+/- littermate was used as the control. Through differential screening of these libraries, over 100 upregulated tumor cDNA fragments were isolated, sequenced and identified with the NCBI BLAST program. From these, we selected genes involved in cellular proliferation, antiapoptosis, and cerebellar differentiation for further analysis. Upregulated genes identified in the human MB library included Unc33-like protein (ULIP), SOX4, Neuronatin (NNAT), the mammalian homologue of Drosophila BarH-like 1(BARHL1), the nuclear matix protein NRP/B (ENC1), and the homeobox OTX2 gene. Genes found to be upregulated in the murine MB library included cyclin D2 (Ccnd2), thymopoietin (Tmpo), Musashi-1 (Msh1), protein phosphatase 2A inhibitor-2 (I-2pp2a), and Unc5h4(D). Using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), the mRNA expression levels for these genes were markedly higher in human MBs than in cerebellum. Western blot analysis was used to further confirm the overexpression of a subset of these genes at the protein level. Notch pathway overactivity was demonstrated in the TE671 MB cell line expressing high levels of MSH1 through HES1-Luciferase transfections. This study has revealed a panel of developmentally regulated genes that may be involved in the pathogenesis of MB.

Cell Line, Tumor↗

PubMed2004

Cloning, characterization and expression of OsGLN2, a rice endo-1,3-beta-glucanase gene regulated developmentally in flowers and hormonally in germinating seeds.

We report here the isolation and characterization of a new endo-1,3-beta-glucanase (1,3-beta-GLU) cDNA, OsGLN2, that is expressed both in flowers and in germinating seeds of rice (Oryza sativa L.). The isolated OsGLN2 gene encoded a protein which displayed 72%, 93% and 92% identity at the amino acid level with those encoded by barley GII, rice Gns4 and glu1 1,3-beta-GLU genes, respectively. A GST-OsGLN2 recombinant protein expressed in Escherichia coli preferentially hydrolyzed Laminaria digitata 1,3;1,6-beta-glucan and liberated only oligosaccharides, suggesting that the enzyme can be classified as a 1,3-beta-GLU. Northern analysis with a 3'-UTR gene-specific probe revealed that OsGLN2 is expressed exclusively in the paleae and lemmas during flowering, and no expression of OsGLN2 was detected in other tissues such as leaf blades, leaf sheaths, stems, nodes and roots in mature rice plants. The OsGLN2 gene is also expressed in germinating seeds, where its expression is predominant in endosperms rather than embryos. In de-embryonated rice half-seeds, addition of gibberellin A3 (GA) greatly enhanced expression of the OsGLN2 gene, while the GA-induced gene expression was suppressed strongly by abscisic acid (ABA). This is the first report, to our knowledge, that OsGLN2 encodes a 1,3-beta-GLU and is expressed specifically in paleae and lemmas during flowering and in germinating seeds, where its expression is enhanced by GA and suppressed by ABA.

Amino Acid Sequence↗

PubMed2002

Seed-specific, developmentally regulated genes of peanut.

Four cDNAs of seed-specific and developmentally regulated peanut ( Arachis hypogaeaL.) genes were identified by differential screening of a peanut-seed cDNA library using cDNA probes constructed from mRNAs isolated from immature and mature stages of the seed. Northern analysis, probed with the four cloned cDNAs, indicated that the genes represented by two cDNAs were expressed abundantly early in seed development, while another two were abundantly expressed later at the cell-expansion stages of seed development. These four genes did not show expression in roots, pegs or leaves. However, one of the early expressed genes was seed coat-specific. One of the clones, Psc11, had significant sequence similarity to subtilisin-like genes in Arabidopsis and soybean. Clones Psc32 and Psc33 had significant similarity to the peanut allergen genes Ara h II and Ara h 6, respectively. The sequence of clone Psc12 was unique and did not show significant similarity to any sequence in the databases. One of the four seed-specific clones showed restriction fragment length polymorphism (RFLP) among peanut lines representing the four peanut botanical varieties. These findings indicate that polymorphism exists in peanut seed-storage genes. This contrasts with other genes previously used for genetic mapping of cultivated peanut.

Journal Article↗

PubMed1998

Isolation of developmentally regulated genes by differential display screening of cDNA libraries.

mRNA differential display RT-PCR has been extensively used for the isolation of genes differentially expressed between RNA populations. We have assessed its utility for the identification of developmentally regulated genes in plasmid cDNA libraries derived from individual tissues dissected from early mouse embryos. Using plasmid Southern blot hybridisation as a secondary screen, we are able to identify such genes and show by whole-mount in situ hybridisation that their expression pattern is that expected from the differential display profile.

Animals↗

PubMed2003

Dictyostelium discoideum developmentally regulated genes whose expression is dependent on MADS box transcription factor SrfA.

The MADS box transcription factor SrfA is required for spore differentiation in Dictyostelium discoideum. srfA null strains form rounded spores that do not resist adverse environmental conditions. Five genes whose expression is dependent on SrfA have been isolated by differential hybridization. One of these genes, sigC, is identical to phg1b, previously characterized in mutants with altered adhesive properties and found to encode a nine-transmembrane-domain protein. This gene is transcribed into two mRNAs as the result of alternative splicing of two internal exons. The slower-migrating mRNA codes for a shorter protein that lacks the first transmembrane fragment and is not expressed in srfA null strains. The other four genes (sigA, sigB, sigD, and 45D) are expressed only during late developmental stages. In situ hybridization experiments showed that expression of sigA, sigB, and sigD is restricted to the sorus of developing structures. sigA codes for a homologue of malate dehydrogenase that converts pyruvate to malate to replenish the tricarboxylic acid cycle. sigB encodes a protein with significant similarity to the GP63 metalloproteinase of Leishmania, leishmanolysin. The sequence of SigD is highly similar to that of several spore coat proteins of D. discoideum, and it may play a role in that structure. The gene 45D codes for an RNA-binding protein homologue whose expression is also dependent on the GATA transcription factor stalky (StkA). The expression of sigB is also dependent on both SrfA and StkA. The expression of 45D, but not of sigA, sigB, sigC, and sigD, can be induced in srfA null cells by constitutive protein kinase A activation. Strains in which either sigA, sigB, or sigD is disrupted were isolated and found to form spores that are not detectably different from those of wild-type strains.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2000

A new developmentally regulated gene family in Leishmania amastigotes encoding a homolog of amastin surface proteins.

The ability of Leishmania to survive within the phagolysosomes of mammalian macrophages is heavily dependent on the developmental regulation of a number of genes. Characterization of genes preferentially expressed during the parasite's intracellular growth would help to elucidate the mechanisms controlling stage-specific gene regulation and the intracellular life of the parasite in general. Using a genomic approach based on the differential hybridization screening of high-density filters, we have identified a new developmentally regulated gene in Leishmania, which is part of a multigene family and encodes a highly hydrophobic protein that shares homology with the Trypanosoma cruzi amastin proteins. The fusion of the Leishmania amastin gene homolog with the green fluorescent protein and analysis by confocal microscopy suggested a surface localization for this protein. The amastin gene homolog is expressed predominantly in the amastigote form of several Leishmania species and is strictly regulated by acidic pH at the post-transcriptional level. Its developmental expression involves sequences within the 3'-untranslated region.

Amino Acid Sequence↗

PubMed1994

DNase I hypersensitive sites far upstream of the rat tryptophan oxygenase gene direct developmentally regulated transcription in livers of transgenic mice.

Expression of the gene coding for tryptophan oxygenase (TO) is switched on in rat liver about two weeks after birth. We identified two clusters of DNaseI hypersensitive (HS) sites in the TO gene upstream region; one near the promoter, the other at a distant upstream location (-8.5 kb). Hypersensitivity of upstream sites was present in adult and in 7 day old rat liver, but absent in kidney. To investigate their role in transcriptional regulation, a reporter gene controlled by both HS site regions was used to generate transgenic mice. In these animals the transgene followed the cell specific and developmental regulation of the endogenous gene: inactive after birth and active in adult liver. Transgenes containing only the promoter proximal HS site were non-functional.

Aging↗

PubMed1995

Isolation and fine mapping of 16 novel human zinc finger-encoding cDNAs identify putative candidate genes for developmental and malignant disorders.

We have isolated and chromosomally fine-mapped 16 novel genes belonging to the human zinc finger Krüppel family (ZNF131-140, 142, 143, 148, 151, 154, and 155), including 1 of the GLI type (ZNF143) and 3 containing a KRAB (Krüppel-associated box) segment (ZNF133, 136, and 140). Based on their map position, several of these ZNF genes are putative candidate genes for both developmental and malignant disorders: ZNF138, ZNF139, and ZNF143 were localized to 7q11.2, 7q21.3-q22.1, and 11p15.3-p15.4, regions involved in deletions and/or translocations associated with Williams syndrome, split hand and foot disease (SHFD1), and Beckwith-Wiedemann syndrome, respectively. ZNF133 was localized to 20p11.2, close to, but probably distinct from, the region deleted in Alagille syndrome. Zinc finger genes mapping to regions commonly deleted in solid tumors included ZNF132, 134, 135, 137, 154, and 155, all located on 19q13 (thyroid adenoma), and ZNF151, at 1p36.1-p36.2 (neuroblastoma, colon cancer, and other tumors). In addition, several of the ZNFs mapped to regions implicated in recurrent chromosomal rearrangements in hematological malignancies (ZNF139, 7q21.3-q22.1; ZNF148, 3q21-q22; ZNF151, 1p36.1-p36.2). The study indicates that the number of ZNF genes in human is large and that systematic isolation and mapping of ZNF genes is a straightforward approach for the identification of novel candidate disease genes.

Abnormalities, Multiple↗

PubMed2005

Molecular cloning of developmentally specific genes by representational difference analysis during the fruiting body formation in the basidiomycete Lentinula edodes.

To understand molecular mechanisms of the fruiting body development in basidiomycetes, we attempted to isolate developmentally regulated genes expressed specifically during the fruiting body formation of Lentinula edodes (Shiitake-mushroom). cDNA representational difference analysis (cDNA-RDA) between vegetatively growing mycelium and two developmental substages, primordium and mature fruiting body, resulted in an isolation of 105 individual genes (51 in primordium and 54 in mature fruiting body, respectively). A search of homology with the protein databases and two basidiomycetous genomes in Phanerochaete chrysosporium and Coprinopsis cinerea revealed that the obtained genes encoded various proteins similar to those involved in general metabolism, cell structure, signal transduction, and responses to stress; in addition, there were apparently several metabolic pathways and signal transduction cascades that could be involved in the fruiting body development. The expression products of several genes revealed no significant homologies to those in the databases, implying that those genes are unique in L. edodes and the encoding products may possess possible functions in the course of fruiting body development. RT-PCR analyses revealed that 20 candidates of the obtained genes were specifically or abundantly transcribed in the course of the fruiting body formation, suggesting that the obtained genes in this work play roles in fruiting body development in L. edodes.

Agaricales↗

PubMed1999

Wild-type and mutant alleles of the Aspergillus nidulans developmental regulator gene brlA: correlation of variant sites with protein function.

The DNA sequences of two wild-type and eleven mutant alleles of the developmental regulator gene brlA from Aspergillus nidulans, which encodes a zinc-finger protein, were characterized. Variant sites were located on rescued plasmids or PCR products based either on their meiotic map position or the use of denaturing gradient gel electrophoresis. Mutations in three null mutants, one of which is partially suppressible, encode premature stop codons. Two environmentally sensitive mutants were characterised by substitution of leucines required for stabilisation of alpha-helices in each of the two putative zinc-finger domains. A third zinc-finger substitution is predicted to disrupt recognition of a guanine residue in the DNA target. The mutations in four other leaky mutants map C-terminal to the zinc fingers; one minimally leaky mutant has a premature stop codon, which results in the removal of the last 38 residues of the protein product.

Alleles↗

PubMed1989

A developmentally regulated gene of trypanosomes encodes a homologue of rat protein-disulfide isomerase and phosphoinositol-phospholipase C.

We have isolated and characterized a developmentally regulated gene in Trypanosoma brucei, arbitrarily termed BS2. BS2 mRNA is substantially more abundant in bloodstream-form trypanosomes than in procyclic culture forms. Its nucleotide sequence reveals a single contiguous open-reading frame of 497 codons and is predicted to encode a protein of approximately 55.5 kilodaltons. A search of the NBRF protein data base revealed that within the predicted amino acid sequence are two of the evolutionarily conserved redox sites typified by thioredoxin of bacteria. Of this family of proteins, the recently sequenced rat genes encoding protein-disulfide isomerase (PDI) and form I phosphoinositide-specific phospholipase C (PIPLC) showed homology extending over the length of all three proteins (i.e., between BS2, PDI, and PIPLC). Although this homology includes the acidic C-terminus characteristic of proteins localized to the lumen of the endoplasmic reticulum, the BS2 product is predicted to possess multiple sites for N-linked glycosylation while PDI and PIPLC have none. Possible roles of the BS2 gene product in trypanosome physiology are discussed.

Amino Acid Sequence↗

PubMed2003

Alternative 5' exons of the CFTR gene show developmental regulation.

The cystic fibrosis transmembrane conductance regulator (CFTR) gene shows a complex mechanism of tissue-specific and temporal regulation. Expression of the sheep and human CFTR genes shows a gradual decline during lung development, from the early mid-trimester through to term. Alternative upstream exons of CFTR have been identified in several species but their functional role remains obscure. We identified a novel 5' exon of the sheep CFTR gene (ov1a) that occurs in two splice forms (ov1aL and ov1aS), which are both mutually exclusive with exon 1. CFTR transcripts including ov1aL and ov1aS are present at low levels in many sheep tissues, however ov1aS shows temporal and spatial regulation during fetal lung development, being most abundant when CFTR expression levels start to decline. Alternative 5' exons -1a and 1a in the human CFTR gene also show changes in expression levels through lung development. Evaluation of ov1aL and ov1aS by Mfold reveals the potential to form extremely stable secondary structures which would cause ribosomal subunit detachment. Further, the loss of exon 1 from the CFTR transcript removes motifs that are crucial for normal trafficking of the CFTR protein. Recruitment of these alternative upstream exons may represent a novel mechanism of developmental regulation of CFTR expression.

Alternative Splicing↗

PubMed2001

Genomic structure of the mouse PP4 gene: a developmentally regulated protein phosphatase.

Protein phosphatases play important roles in the control of various cellular processes. Here, we report the cloning and characterization of the murine cDNA and genomic DNA encoding the serine/threonine protein phosphatase 4 (PP4), also called PPX. While the nucleotide sequences of murine and human PP4 are distinct, their amino acid sequences are identical. We have analyzed the protein, cDNA and genomic PP4 sequences to provide insight into the structure, function and potential regulation of PP4. Genomic Southern blots demonstrated the conservation of PP4 across species. Using Northern blotting and in situ hybridization, we have examined the expression of PP4 in murine embryos and adult tissues. In adult tissues, PP4 was expressed at high levels in the testis, kidney, liver, and lung, and at lower levels in virtually all tissues. PP4 was differentially expressed in murine embryos at different developmental stages, suggesting that PP4 is a developmentally regulated protein phosphatase.

Amino Acid Sequence↗