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At least 217 records · Page 12Linked to original sources
PubMed2000

Aberrant folate response and premature development in a mutant of Dictyostelium discoideum.

Growth and development are mutually exclusive in Dictyostelium discoideum. The transition between the two stages of the life cycle is regulated by the relative abundance of nutrients and proteins secreted by the cells which reflect population density. At the transition from growth to development, the discoidin genes--developmental markers--are induced by the "quorum" protein PSF. The effect of PSF is counteracted by food bacteria and by folate [8]. We show that folate treatment during growth delays morphologic development. Furthermore, we demonstrate that in a mutant of Dictyostelium discoideum (V188, renamed HBW3), which expresses discoidinI during growth and which develops rapidly [46], discoidinI expression is less sensitive to folate than in wild type cells. Finally, we present evidence that fragments of the discoidinI gamma promoter which are unresponsive to PSF and CM are sufficient for misregulation in the mutant. The only known regulator of these promoter elements is folate. Changes in the expression of other early developmental genes are also shown. Taken together, these data suggest that the reduced sensitivity to folate might be the cause for the "rapid development" phenotype of the mutant and that folate regulates developmental timing.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

cDNA libraries from single human preimplantation embryos.

In this paper, the construction, evaluation, and application of cDNA libraries from eight unfertilized oocytes and single four-cell-, seven-cell-, and blastocyst-stage embryos are described. Rapid, reproducible, and efficient procedures for the construction of PCR-based cDNA libraries from fewer than 10 cells were first developed in small populations of fibroblast cells. The human embryo libraries display complexities sufficient (between 10(5) and 10(6) clones) to represent the entire active gene population at these early stages of human development. The ubiquitous cytoskeletal elements, beta-actin, keratin-18, and alpha-tubulin, were detected at the expected frequency. Sequencing of consecutively picked random clones, without selection, showed the presence of a variety of sequences, such as the human transposable element, LINE-1 and Alu repeat sequences, housekeeping genes, and tissue-specific genes, such as alpha-globin and FMR-1. In addition to cDNAs corresponding to known ESTs (expressed sequence tags) in the GenBank and dbEST databases, a high proportion of novel sequences were detected. Applications of the libraries to several areas of interest, such as expression of CpG-island-containing "tissue-specific" genes, developmental genes expressed in a stage-specific manner, and a search for monoallelic expression of imprinted genes, are described. The libraries are a valuable resource for the study of gene expression during human preimplantation development and obviate the need for research on the human embryos themselves.

Cells, Cultured↗
PubMed1992

Isolation and characterization of the human sucrase-isomaltase gene and demonstration of intestine-specific transcriptional elements.

The molecular mechanisms that regulate intestine-specific gene expression and the transition from proliferating, undifferentiated crypt cells to nonproliferating, differentiated villus cells are unknown. Sucrase-isomaltase is an apical membrane disaccharidase that is found exclusively in enterocytes of adult intestine and is expressed in a complex pattern along the intestinal crypt-villus axis. To investigate the regulation of sucrase-isomaltase, we have cloned and sequenced 3.6 kilobases of the 5'-flanking region of the human sucrase-isomaltase gene. The transcriptional start site was mapped in human small intestine and in a colonic adenocarcinoma cell line (Caco-2) using an anchored polymerase chain reaction, primer extension, and RNase protection assays. The 5'-flanking DNA of the gene was linked to either chloramphenicol acetyltransferase or luciferase reporter genes and used for transfection into Caco-2, HeLa, and HepG2 cells. This analysis demonstrated that intestine-specific transcription of the sucrase-isomaltase gene involves both proximal and distal regulatory elements. Use of sucrase-isomaltase as a model gene will allow investigation of the mechanisms that regulate transcription of enterocyte-specific genes, developmental gene expression in the small intestine and colon, and the process of differentiation as epithelial cells migrate from intestinal crypts onto the villus in adult intestine.

Adenocarcinoma↗
PubMed1995

A large-scale gene-trap screen for insertional mutations in developmentally regulated genes in mice.

We have used a gene-trap vector and mouse embryonic stem (ES) cells to screen for insertional mutations in genes developmentally regulated at 8.5 days of embryogenesis (dpc). From 38,730 cell lines with vector insertions, 393 clonal integrations had disrupted active transcription units, as assayed by beta-galactosidase reporter gene expression. From these lines, 290 clones were recovered and injected into blastocysts to assay for reporter gene expression in 8.5-dpc chimeric mouse embryos. Of these, 279 clones provided a sufficient number of chimeric embryos for analysis. Thirty-six (13%) showed restricted patterns of reporter-gene expression, 88 (32%) showed widespread expression and 155 (55%) failed to show detectable levels of expression. Further analysis showed that approximately one-third of the clones that did not express detectable levels of the reporter gene at 8.5 dpc displayed reporter gene activity at 12.5 dpc. Thus, a large proportion of the genes that are expressed in ES cells are either temporally or spatially regulated during embryogenesis. These results indicate that gene-trap mutageneses in embryonic stem cells provide an effective approach for isolating mutations in a large number of developmentally regulated genes.

Animals↗
PubMed1981

The cuticle genes of drosophila: a developmentally regulated gene cluster.

A 36 kilobase (kb) DNA segment of the Drosophila genome that contains several larval cuticle protein genes has been cloned and characterized. This segment maps at chromosomal locus 44D. It contains five genes, all of which are expressed at the same time of Drosophila development. Four of the genes are clustered within 7.9 kb of DNA and are abundantly expressed as poly(A)RNA in the epidermis of late third instar larvae but are not abundantly expressed in other developmental stages. A fifth gene lies 8 kb away from this cluster and is expressed at a much lower level in late third instar larval poly(A) RNA. Three of the four abundantly expressed genes have been shown to code for larval cuticle proteins; less decisive evidence indicates that the fourth gene also probably codes for a larval cuticle protein. Some of the genes are related in DNA sequence, and the proteins encoded in the cluster are related immunologically. Thus the cuticle genes encoded by the segment at 44D are members of a family of genes of common ancestry, which share the same pattern of developmental expression and reside in a small segment of the Drosophila genome.

Animals↗
PubMed2002

Design of an HIV-1 lentiviral-based gene-trap vector to detect developmentally regulated genes in mammalian cells.

The recent development of HIV-1 lentiviral vectors is especially useful for gene transfer because they achieve efficient integration into nondividing cell genomes and successful long-term expression of the transgene. These attributes make the vector useful for gene delivery, mutagenesis, and other applications in mammalian systems. Here we describe two HIV-1-based lentiviral vector derivatives, pZR-1 and pZR-2, that can be used in gene-trap experiments in mammalian cells in vitro and in vivo. Each lentiviral gene-trap vector contains a reporter gene, either beta-lactamase or enhanced green fluorescent protein (EGFP), that is inserted into the U3 region of the 3' long terminal repeat. Both of the trap vectors readily integrate into the host genome by using a convenient infection technique. Appropriate insertion of the vector into genes causes EGFP or beta-lactamase expression. This technique should facilitate the rapid enrichment and cloning of the trapped cells and provides an opportunity to select subpopulations of trapped cells based on the subcellular localization of reporter genes. Our findings suggest that the reporter gene is driven by an upstream, cell-specific promoter during cell culture and cell differentiation, which further supports the usefulness of lentivirus-based gene-trap vectors. Lentiviral gene-trap vectors appear to offer a wealth of possibilities for the study of cell differentiation and lineage commitment, as well as for the discovery of new genes.

Animals↗
PubMed2002

Role of fruA and csgA genes in gene expression during development of Myxococcus xanthus. Analysis by two-dimensional gel electrophoresis.

Two genes, fruA and csgA, encoding a putative transcription factor and C-factor, respectively, are essential for fruiting body formation of Myxococcus xanthus. To investigate the role of fruA and csgA genes in developmental gene expression, developing cells as well as vegetative cells of M. xanthus wild-type, fruA::Tc, and csgA731 strains were pulse-labeled with [(35)S]methionine, and the whole cell proteins were analyzed using two-dimensional immobilized pH gradient/SDS-PAGE. Differences in protein synthesis patterns among more than 700 protein spots were detected during development of the three strains. Fourteen proteins showing distinctly different expression patterns in mutant cells were analyzed in more detail. Five of the 14 proteins were identified as elongation factor Tu (EF-Tu), Dru, DofA, FruA, and protein S by immunoblot analysis and mass spectroscopy. A gene encoding DofA was cloned and sequenced. Although both fruA and csgA genes regulate early development of M. xanthus, they were found to differently regulate expression of several developmental genes. The production of six proteins, including DofA and protein S, was dependent on fruA, whereas the production of two proteins was dependent on csgA, and one protein was dependent on both fruA and csgA. To explain the present findings, a new model was presented in which different levels of FruA phosphorylation may distinctively regulate the expression of two groups of developmental genes.

Amino Acid Sequence↗
PubMed2005

An optimized embryonic stem cell model for consistent gene expression and developmental studies: a fundamental study.

In vitro differentiation of embryonic stem (ES) cells results in generation of tissue-specific somatic cells and may represent a powerful tool for general understanding of cellular differentiation and development in vivo. Culturing of most ES cell lines requires murine embryonic fibroblasts (MEF), which may influence adventitiously the genetic differentiation program of ES cells. We compared the expression profile of key developmental genes in the MEF-independent CGR8 ES cell line and in the MEF-dependent D3 ES cell line. Using neomycin-resistant MEFs we demonstrated that MEFs are able to contaminate the D3 ES cells even after removing the MEFs. Subsequently, optimal differentiation conditions were established for the differentiation of CGR8 ES cells into various germ layer cells. Detailed gene expression studies in differentiating CGR8 cells were done by RT-PCR analysis and by microarray analysis demonstrating a general trend of the assessed genes to be expressed either in 3 days- or 10-days old embryoid bodies (EBs) when compared to undifferentiated ES cells. Subsets within the various functional gene classes were defined that are specifically up- or down-regulated in concert. Interestingly, the present results demonstrate that developmental processes toward germ layer formation are irreversible and mostly independent of the culture conditions. Notably, apoptotic and mitochondrial ribosomal genes were down- and up-regulated in 10-days old EBs, respectively, whereas compared to the 3-days old EBs whereas the activity of the extracellular signal-regulated kinase (ERK) 1/2 decreased with progressive development. This article defines a platform for ES cell differentiation and gene expression studies.

Animals↗
PubMed1994

The BTB domain, found primarily in zinc finger proteins, defines an evolutionarily conserved family that includes several developmentally regulated genes in Drosophila.

The Drosophila bric à brac protein and the transcriptional regulators encoded by tramtrack and Broad-Complex contain a highly conserved domain of approximately 115 amino acids, which we have called the BTB domain. We have identified six additional Drosophila genes that encode this domain. Five of these genes are developmentally regulated, and one of them appears to be functionally related to bric à brac. The BTB domain defines a gene family with an estimated 40 members in Drosophila. This domain is found primarily at the N terminus of zinc finger proteins and is evolutionarily conserved from Drosophila to mammals.

Amino Acid Sequence↗
PubMed2004

Inducible gene trapping with drug-selectable markers and Cre/loxP to identify developmentally regulated genes.

Gene trapping in mouse embryonic stem cells is an important genetic approach that allows simultaneous mutation of genes and generation of corresponding mutant mice. We designed a selection scheme with drug selection markers and Cre/loxP technology which allows screening of gene trap events that responded to a signaling molecule in a 96-well format. Nine hundred twenty gene trap clones were assayed, and 258 were classified as gene traps induced by in vitro differentiation. Sixty-five of the in vitro differentiation-inducible gene traps were also responsive to retinoic acid treatment. In vivo analysis revealed that 85% of the retinoic acid-inducible gene traps trapped developmentally regulated genes, consistent with the observation that genes induced by retinoic acid treatment are likely to be developmentally regulated. Our results demonstrate that the inducible gene trapping system described here can be used to enrich in vitro for traps in genes of interest. Furthermore, we demonstrate that the cre reporter is extremely sensitive and can be used to explore chromosomal regions that are not detectable with neo as a selection cassette.

Animals↗
PubMedDate not supplied

[How to construct a neural tube: molecular genetics of neuro-embryological development].

INTRODUCTION: The 'new neuroembryology' combines classical morphogenesis with new molecular genetic data on the programming of neural differentiation and the interactions of transcription products of various developmental genes. DEVELOPMENT: The neuroepithelium is generated from the primitive (Hensen's) node in birds and mammals, homologous with the dorsal lip of the amphibian gastula. The developing neural placode is 'induced' by the notochord, which initiates the differentiation of the floor plate, a ventral midline ependyma. This induction is effected by a gene called Sonic hedgehog, which also is a strong ventralizing influence and induces motor neuron differentiation. Various families of genes program neural tube differentiation with dorsoventral or ventrodorsal gradients, rostrocaudal gradients and mediolateral gradients. Genes that establish the primordial axes of differentiation are 'organizer genes' and those involved with the identity of specific structures are 'regulatory genes'. Some developmental genes continue to be expressed in adult life and preserve the unique identity of specific cellular types. The neural tube is divided into compartments or segments known as neuromeres (or rhombomeres in the hindbrain) with physical and chemical barriers that limit cell migration between segments; the entire spinal cord is formed from rhombomere 8. Both extrinsic and intrinsic mechanical factors contribute to bend the neural placode to form the neural tube [REV NEUROL 1999; 28: 110-6].

Animals↗
PubMed1996

Severe congenital limb deficiencies, vertebral hypersegmentation, absent thymus and mirror polydactyly: a defect expression of a developmental control gene?

We describe two unrelated patients with a complex malformation pattern that may be a candidate for a developmental gene disorder. These two patients had severe, symmetrical upper and lower limb deficiencies, vertebral hypersegmentation, and duodenal atresia. Patient 1 also had mirror-image polydactyly of his feet; patient 2 was athymic. The concurrence in two unrelated patients of additional vertebrae with severe anomalies in limb development, including a symmetrical deficiency of the four limbs and either mirror-image duplication of some toes (only in patient 1) or absence of the thymus (only in patient 2), represents an early alteration in body-plan organization. Since limb development, thymus development and segmentation are possibly under the control of homeobox genes in the human embryo, it seems reasonable that the malformations observed in these two patients resulted from a defect of a gene controlling developmental pattern formation, possibly a homeobox gene or a paired-box gene. Severe limb deficiencies have been reported in other well-known genetic entities, such as Roberts syndrome, Baller-Gerold syndrome, X-linked amelia, and DK-phocomelia syndrome. However, since the specific pattern of anomalies observed in these patients makes the diagnosis of some of the abovementioned disorders unlikely, we conclude that our patients have a previously undescribed disorder.

Abnormalities, Multiple↗
PubMed2001

Analysis of developmentally regulated genes of the parasite Haemonchus contortus.

Differential regulation of gene expression in the development of Haemonchus contortus was analysed using RNA arbitrarily-primed PCR. A study of third-stage larval and adult H. contortus revealed large differences between the two stages; 32 and 30% unique third-stage larval and adult RNA arbitrarily-primed PCR products, respectively. This finding is consistent with a high degree of differential gene expression between these developmental stages. A number of adult products were sequenced, revealing 11 molecules to be similar to deposits within sequence databases. Four other molecules that did not have significant similarity to sequences in the databases may represent developmentally regulated genes specific to H. contortus. Northern analysis of the putative adult-expressed molecules with homologues in the databases confirmed that four were expressed only in adults, while four were expressed in both stages, but had different sized transcripts. This may reflect differential splicing, or expression of closely related but different molecules at different life cycle stages. Two molecules were present in mRNA populations from both stages, suggesting these were false stage-associated molecules. No transcript was detected for one molecule by Northern analysis, probably due to low level of expression. In situ hybridisation analysis was used to localise expression of transcripts in the adult parasite, in particular, to gain some insight into the nature of those molecules with no known predicted function.

Amino Acid Sequence↗
PubMed2000

Developmental regulatory genes and echinoderm evolution.

Modified interactions among developmental regulatory genes and changes in their expression domains are likely to be an important part of the developmental basis for evolutionary changes in morphology. Although developmental regulatory genes are now being studied in an increasing number of taxa, there has been little attempt to analyze the resulting data within an explicit phylogenetic context. Here we present comparative analyses of expression data from regulatory genes in the phylum Echinodermata, considering the implications for understanding both echinoderm evolution as well as the evolution of regulatory genes in general. Reconstructing the independent evolutionary histories of regulatory genes, their expression domains, their developmental roles, and the structures in which they are expressed reveals a number of distinct evolutionary patterns. A few of these patterns correspond to interpretations common in the literature, whereas others have received little prior mention. Together, the analyses indicate that the evolution of echinoderms involved: (1) the appearance of many apomorphic developmental roles and expression domains, some of which have plesiomorphic bilateral symmetry and others of which have apomorphic radial symmetry or left-right asymmetry; (2) the loss of some developmental roles and expression domains thought to be plesiomorphic for Bilateria; and (3) the retention of some developmental roles thought to be plesiomorphic for Bilateria, although with modification in expression domains. Some of the modifications within the Echinodermata concern adult structures; others, transient larval structures. Some changes apparently appeared early in echinoderm evolution (> 450 Ma), whereas others probably happened more recently (< 50 Ma). Cases of likely convergence in expression domains suggest caution when using developmental regulatory genes to make inferences about homology among morphological structures of distantly related taxa.

Animals↗
PubMed1997

In vitro preselection of gene-trapped embryonic stem cell clones for characterizing novel developmentally regulated genes in the mouse.

We have developed an in vitro gene trap screen for novel murine genes that allows one to determine, prior to making chimeric or transgenic animals, if these genes are expressed in one or more specific embryonic tissues. Totipotent embryonic stem (ES) cells are infected with a retroviral gene trap construct encoding a selectable lacZ/neo fusion gene, which is expressed only if the gene trap inserts within an active transcription unit. G418-resistant ES cell clones are induced to differentiate in vitro, and neurons, glia, myocytes, and chondrocytes are screened for expression of beta-galactosidase (beta-gal). cDNAs of the gene trap transcripts are obtained by 5' rapid amplification of cDNA ends and are sequenced to determine if they represent novel genes. In situ hybridization analyses show that trapped genes are expressed in vivo within the cell types that express beta-gal in vitro. Gene traps and their wild-type alleles are characterized in terms of copy number, alternate splicing of their transcripts, and the proportion of endogenous mRNA sequence that is replaced by lacZ/neo in the hybrid gene trap transcript. This approach, which we term "in vitro preselection," is more economical than standard in vivo gene trap screening because tissue-specific expression of probable knockout alleles is verified before transgenic animals are generated. These results also highlight the utility of ES cell differentiation in vitro as a method with which to study the molecular mechanisms regulating the specification and commitment of a variety of cell and tissue types.

Animals↗
PubMed1998

Characterization of SCML1, a new gene in Xp22, with homology to developmental polycomb genes.

Using exon trapping, we have identified a new human gene in Xp22 encoding a 3-kb mRNA. Expression of this RNA is detectable in a range of tissues but is most pronounced in skeletal muscle and heart. The gene, designated "sex comb on midleg-like-1" (SCML1), maps 14 kb centromeric of marker DXS418, between DXS418 and DXS7994, and is transcribed from telomere to centromere. SCML1 spans 18 kb of genomic DNA, consists of six exons, and has a 624-bp open reading frame. The predicted 27-kDa SCML1 protein contains two domains that each have a high homology to two Drosophila transcriptional repressors of the polycomb group (PcG) genes and their homologues in mouse and human. PcG genes are known to be involved in the regulation of homeotic genes, and the mammalian homologues of the PcG genes repress the expression of Hox genes. SCML1 appears to be a new human member of this gene group and may play an important role in the control of embryonal development.

Amino Acid Sequence↗
PubMed2000

Multiple paralogous genes related to the Streptomyces coelicolor developmental regulatory gene whiB are present in Streptomyces and other actinomycetes.

The whiB sporulation gene of Streptomyces coelicolor was shown [Davis, N. K. & Chater, K. F. (1992). Mol Gen Genet 232, 351-358] to encode a small, cysteine-rich putative transcription factor unlike any that had been described previously. The large database of DNA sequences of mycobacteria (like Streptomyces, members of the Actinomycetales) has revealed a family of genes encoding proteins related to WhiB. Mycobacterium tuberculosis contains at least six such genes (whiB homologues in mycobacteria: whmA-F) and a likely seventh, whmG. Using conserved features of Whm proteins, a PCR-based approach led to the discovery that S. coelicolor A3(2) contains several similar genes. Cloning and sequencing of these whiB-like (wbI) genes revealed likely orthologues of four of the whm genes of M. tuberculosis. In all, S. coelicolor contains at least five wbI genes in addition to whiB itself. All five were shown by RT-PCR to be transcribed. A Southern blotting survey using each wbI gene as a probe showed that nearly all of a series of representatives of ten actinomycete genera (including morphologically simple organisms) contain close homologues of several wbI genes, suggesting that the ancient progenitor of all these organisms already contained a family of such genes, which have not been found in any other organisms.

Actinomycetales↗