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At least 19 recordsLinked to original sources
PubMed1995

Identification of the minimum regulatory region of a Myxococcus xanthus A-signal-dependent developmental gene.

Developmental expression of the Myxococcus xanthus gene 4521 requires extracellular A-signal. This signal is generated in response to nutrient limitation and functions in cell density sensing. To identify the upstream limit of the minimum region required in vivo for A-signal-dependent 4521 expression, a 5' deletion analysis of the 4521 regulatory region was performed. A new vector, pHBK280, was designed to facilitate this analysis. This vector creates tandem copies of the 4521 gene in the M. xanthus chromosome, such that the regulatory region to be tested is upstream of a single copy of the lacZ reporter gene. The 5' deletion analysis revealed that at most, 146 bp of DNA upstream of the transcription start site (TSS) was required for full developmental expression of 4521. Basal expression levels were observed with constructions containing 90 bp of DNA upstream of the TSS. In vitro gel retardation assays revealed that DNA fragments with 5' ends of 146 and 125 bp upstream of the TSS and a common 3' end of +24 bp were retarded in their mobility after incubation with all of the M. xanthus developmental crude cell extracts tested. In contrast, a fragment starting at 90 bp upstream of the TSS and ending at +24 bp was not retarded in its mobility after incubation with the same cell extracts. These in vivo and in vitro data suggest that cis-acting elements located between 146 and 90 bp upstream of the TSS serve as binding sites for one or more trans-acting regulatory factors required for 4521 developmental expression.

Bacterial Proteins↗
PubMed2000

Abnormal RNA expression of 11p15 imprinted genes and kidney developmental genes in Wilms' tumor.

Wilms' tumor (WT) is caused by abnormal development of embryonal kidney cells. WT cells are frequently affected by deletions or functional inactivation of maternal alleles at chromosome 11p15, which indicates that the loss of maternally expressed genes in this region plays an important role in WT pathogenesis. Maternally expressed genes indeed exist within an imprinted region at 11p15.5. Among these, BWR1C is highly expressed in fetal but not in adult kidney, which suggests that it may fulfil an important role in kidney development. Here, we demonstrate that the lack of BWR1C expression is common in WT. Its homology with the proapoptotic gene TDAG51 suggests that the loss of BWR1C expression may be relevant in WT development. In addition, the analysis of the expression of other 11p15 imprinted genes and kidney-developmentally regulated genes indicates that IGF2 overexpression, inappropriate coexpression of RET and GDNF and, in some cases, down-regulation of CDKN1C may also play an important role in the pathogenesis of WT. Our results add new elements to the understanding of the biological basis of WT, which may have implications for WT diagnosis and therapy.

Adult↗
PubMed1998

From genes to individuals: developmental genes and the generation of the phenotype.

The success of the genetic approach to developmental biology has provided us with a suite of genes that are involved in the regulation of ontogenetic pathways. It is therefore time to ask whether and how such genes might be involved in the generation of adaptive phenotypes. Unfortunately, the current results do not provide a clear answer. Most of the genes that have been studied by developmental biologists affect early embryonic traits with significant effects on the whole organism. These genes are often highly conserved which allows us to do comparative studies even across phyla. However, whether the same genes are also involved in short-term ecological adaptations remains unclear. The suggestion that early acting ontogenetic genes may also affect late phenotypes comes from the genetic analysis of quantitative traits like bristle numbers in Drosophila. A rough mapping of the major loci affecting these traits shows that these loci might correspond to well known early acting genes. On the other hand, there are also many minor effect loci that are as yet uncharacterized. We suggest that these minor loci might correspond to a different class of genes. In comparative studies of randomly drawn cDNAs from Drosophila we find that there is a large group of genes that evolve fast and that are significantly under-represented in normal genetic screens. We speculate that these genes might provide a large, as yet poorly understood, reservoir of genes that might be involved in the evolution of quantitative traits and short-term adaptations.

Adaptation, Physiological↗
PubMed1997

Ascidian actin genes: developmental regulation of gene expression and molecular evolution.

Actin is a ubiquitous protein in eukaryotic cells and plays an important role in cell structure, cell motility, and the generation of contractile force in both muscle and nonmuscle cells. Multiple genes encoding muscle or nonmuscle actins have been isolated from several species of ascidians and their expression patterns have been investigated. Sequence and expression analyses of muscle actin genes have shown that ascidians have at least two distinct isoforms of muscle actin, the larval muscle and body-wall isoforms. In the ascidian Halocynthia roretzi, two clusters of actin genes are expressed in the larval muscle cells. The HrMA2/4 cluster contains at least five actin genes and the HrMA1 cluster contains a pair of actin genes whose expression is regulated by a single bidirectional promoter. cis-Regulatory elements essential for muscle-specific expression of a larval muscle actin gene HrMA4a have been identified. The adult body-wall muscle actin is clearly distinguished from the larval muscle actin by diagnostic amino acids. The adult muscle actin genes may be useful tools to investigate the mechanisms of muscle development in ascidian adults. The evolution of chordate actin genes has been inferred by comparing the organization and sequences of actin genes and performing molecular phylogenetic analysis. The results suggest a close relationship between ascidian and vertebrate actins. The chordate ancestor seems to have evolved the "chordate-type" cytoplasmic and muscle actins before its divergence into vertebrates and urochordates. The phylogenetic analysis also suggests that the vertebrate muscle actin isoforms evolved after the separation of the vertebrates and urochordates. Muscle actin genes have been used to investigate the mechanism of muscle cell regression during the evolution of anural development. The results suggest that the regression of muscle cell differentiation is mediated by changes in the structure of muscle actin genes rather than in the trans-acting regulatory factors required for their expression. Actin genes have provided a unique system to study developmental and evolutionary mechanisms in chordates.

Actins↗
PubMed1998

Efficient gene trap screening for novel developmental genes using IRES beta geo vector and in vitro preselection.

We have used different gene trap vectors and in vitro preselection of embryonic stem (ES) cells for a large scale screening of insertional mutations in developmentally regulated genes. A gene trap vector was constructed, which contains an internal ribosome entry site (IRES) upstream from a betageo selectable-reporter fusion gene. Analysis of 801 independent integrations revealed that the IRESbetageo vector allows for a global enrichment of about 15 folds in the number of detectable gene trap events when compared with a conventional betageo vector. Characterization of in vitro and in vivo lacZ expression suggested that this IRES-based vector is able to capture a wide range of genes expressed in a variety of tissues and developmental stages, and it can also allow trapping of genes expressed at very low levels in ES cells. A preselection protocol was devised, where gene-trapped ES cells were grown in the presence of specific growth/differentiation factors such as follistatin, nerve growth factor, and retinoic acid. Several gene trap integrations were found to be either activated or repressed by one of these factors. Characterization of lacZ expression during embryogenesis showed a strong enrichment of restricted patterns in vivo after ES cell preselection. These results suggest that a combination of IRESbetageo vector and in vitro preselection is more effective for the capture and mutation of a large number of developmental genes.

Animals↗
PubMed1999

Silencing of developmental genes in Hydra.

Numerous developmental control genes have been isolated in a variety of organisms by either homology cloning or system-specific strategies. Functional genetic tests, however, are available for only a few model organisms and particularly are missing in a number of animals that occupy key positions for understanding the evolution of development and gene function. Double-stranded RNA-mediated interference (RNAi) opens a way to perform functional studies in such "nongenetic" organisms. Here we show that RNAi can be used to test the function of developmental genes in the cnidarian Hydra, a classical model for developmental studies. Introduction of double-stranded RNA corresponding to the head-specific gene ks1 caused strong depletion of ks1 transcripts. ks1 loss-of-function polyps exhibited severe defects in head formation, indicating an important role of ks1 in Hydra head development. Our results demonstrate for the first time efficient gene silencing in Hydra. RNAi provides an entry point for a variety of functional studies and a direct approach for analyzing the hierarchy of regulatory genes in Hydra, which until now has not been amenable to loss-of-function genetics.

Animals↗
PubMed1992

Genetic linkage analysis of the murine developmental mutant velvet coat (Ve) and the distal chromosome 15 developmental genes Hox-3.1, Rar-g, Wnt-1, and Krt-2.

We have identified restriction fragment length polymorphisms between Mus musculus and Mus spretus for the Chromosome 15 loci Hox-3, Wnt-1, Krt-2, Rar-g, and Ly-6. We followed the inheritance of these alleles in interspecific genetic test crosses between velvet coat (Ve) heterozygotes and M. spretus. The results suggest a gene order and recombination distances (in cM) of Ly-6-22-Wnt-1-2-Ve/Krt-2/Rar-g-3-Hox-3. No recombination was found between Ve, Krt-2, and Rar-g. The data also provide evidence for the hypothesis of a large-scale genomic duplication involving homologous gene pairs on mouse Chromosomes 15 and 11.

Animals↗
PubMed1997

DNA methylation and developmental genes in lymphomagenesis--more questions than answers?

There is now considerable evidence suggesting that alterations in the DNA methylating machinery play an important role in tumorigenesis and tumour progression. For example, focal hypermethylation and generalised genomic demethylation are features of many different types of neoplasms. It is thought that tumorigenesis and tumour progression may be caused by hypermethylation induced mutational events and silencing of genes which control cellular proliferation and/or demethylation induced reactivation of genes which may only be required during embryological development. Consequently, we have begun to investigate the role of DNA methylation and developmental genes in malignant lymphoproliferative diseases. Previously, in all cases of non-Hodgkins lymphoma and leukemia studied, we have shown that the myogenic developmental gene Myf-3 is abnormally hypermethylated. In this review we discuss the possible significance of these findings since in vitro studies suggest that Myf-3 may play an important role in control of the cell cycle and therefore lymphomagenesis. In vitro and in vivo evidence suggests that PAX genes may also have oncogenic potential. The PAX family of developmental genes are involved in cellular differentiation, proliferation and cell migration. Expression of PAX3 in particular is associated with cellular mobility. Our previous studies have indicated that alternate regional expression of PAX genes may be controlled by DNA methylation. Therefore, we have proposed that abnormal methylation profiles of PAX3 may be associated with neoplastic transformation and/or metastatic potential. Results thus far reveal that the paired box of PAX3 is abnormally hypermethylated and the homeobox abnormally hypomethylated in lymphomas and leukemias. These new findings are consistent with our postulate and support the idea that inappropriate methylation induced activation or inactivation of developmental genes such as Myf-3 and PAX3 play an important role in lymphomagenesis and disease progression and that inspection of the methylation status of other developmental genes is warranted.

Animals↗
PubMed1997

[Developmental genes].

In the present review article, we have attempted to define and class the so called "developmental genes". This designation applies to genes whose activity is involved in lineage determination, in differentiation pathways or in the modes of tissue or organ formation. A special emphasis has been given to genes controlling the body plan in the course of development. Three main subclasses of such genes are described: genes involved in very early development by establishing the anteroposterior or dorso-ventral axes of the embryo (or of the insect larva); segmentation genes; homeotic genes containing an homeodomain (HD) motif and homeotic-related genes (with a "LIM" or "PAX" motif). While classical (HD containing) homeotic genes were initially discovered and studied in drosophila, their general occurrence in many other species, particularly in vertebrates was soon reported. They are characterized phylogenetically speaking, by a high degree of sequence similarities and chromosomal organization, although their number appears much greater in vertebrates than in insects due to successive duplication and chromosomal distribution events. In vertebrates they are essentially involved in the development of the central nervous system. Large varieties of genes with "LIM" or "PAX" motifs have been reported, and many subclasses can be distinguished depending upon the presence or absence of distinct peptidic motifs within the genes under concern. The peptidic domains encoded by the LIM motifs include "Zn finger" containing varieties which are involved in protein-protein interactions. The roles of genes with a LIM motif vary according to the type of sub-variety (organization of the central nervous system; axonal distribution of peripheric nerves at distinct levels of the spinal cord, control of tissue differentiation, etc.). "Pax" genes include a DNA binding domain (encoded by the "paired" motif) with variable sequences and organization, which is sometime in the vicinity of an homeodomain. Generally speaking "Pax" genes behave like controlling elements in the development of the brain or of tissues derived from the neural crest.

Animals↗
PubMed1997

Multiple sclerosis: re-expression of a developmental gene in chronic lesions correlates with remyelination.

Central nervous system tissue from multiple sclerosis and non-multiple sclerosis subjects was studied for the expression of exon 2 myelin basic protein gene products at the protein and message levels by immunocytochemistry and in situ hybridization, respectively. The exon 2-encoded protein sequence is normally expressed during development (myelination) within the 21.5- and 20.2-kd isoforms of myelin basic protein and is downregulated in the adult central nervous system where the 18.5- and 17.2-kd isoforms predominate, the latter devoid of exon 2 owing to alternative splicing. Exon 2 myelin basic protein gene products were readily demonstrable in multiple sclerosis samples, the highest levels correlating with remyelination in chronic lesions while normal adult central nervous system and non-multiple sclerosis material showed very low levels and fetal human central nervous system tissue (a positive control) showed high levels. We conclude that recapitulation of ontogenetic events during myelin repair accounts for the increased expression of the exon 2-encoded protein sequence in the adult central nervous system during multiple sclerosis, an event that might underly the previously observed T-cell activation to this protein sequence during relapses.

Acute Disease↗
PubMed2000

Fetal lung development: airway pressure enhances the expression of developmental genes.

BACKGROUND/PURPOSE: The mechanisms by which static airway pressures in the developing lung affect development are unknown. The in vitro murine fetal lung model with airway ligation reproduces the phenomenon of intraluminal airway pressure in developing lungs. We have applied the technique of differential display of mRNAs to fetal murine lungs that were maintained in organ culture with and without tracheal ligation. The goal of this investigation was to identify genes that are induced or enhanced by airway pressure during lung development. METHODS: Fetuses were harvested from CD-1 mice on gestational day (Gd) 14. The lungs were removed and trachea either transected or ligated and organ cultured for 7 days. Total RNA was extracted from cultured unligated controls and ligated lungs. Reverse transcription (RT) of the purified total RNA from each pooled sample was performed with anchor primer H-T11G or C and one of 24 arbitrary primers followed by polymerase chain reaction (PCR) of the RT mixtures. PCR products were electrophoresed on a DNA sequencing gel. Differentially expressed cDNA bands of interest were cut from the dried gel. Each cDNA was then reamplified. Reamplified cDNAs were extracted, PCR amplified, cloned, and sequenced for homology to existing sequences in the GenBank database. RESULTS: Sequencing identified 4 differentially expressed genes enhanced by tracheal ligation: hepatoma-derived growth factor (HDGF), ribosomal protein S24, stathmin, and parathyroid hormone (PTH). CONCLUSIONS: Genes enhanced by airway pressure or tracheal ligation are mitogenic for fibroblasts, correlate with cell proliferation, regulate cell proliferation and differentiation, and may play a role in growth in distal lung and type II cell differentiation. Further work is necessary to identify the mechanisms by which these genes influence lung maturational processes.

Aniline Compounds↗
PubMedDate not supplied

The Drosophila developmental gene snail encodes a protein with nucleic acid binding fingers.

Pattern formation in the Drosophila embryo requires the concerted expression of maternal and zygotic genes. At least nineteen genes, twelve of which are maternally expressed, are involved in the establishment of dorsal-ventral polarity. Mutations in any one of these genes result in distinct alterations of cell fates and in the formation of an abnormal dorsal-ventral pattern. Mutants of the 'dorsal group', eleven of the maternal genes, have a common recessive phenotype similar to that described for dorsal, in that cells located at ventral and lateral positions assume dorsal fates and ventral structures fail to develop. Thus the dorsal group gene products may be involved in the establishment of a gradient of positional information along the dorsal-ventral axis. We have cloned snail (sna), a zygotic gene, whose expression is essential for the correct specification of dorsal-ventral pattern. In this report, we present evidence that the complementary DNA-deduced protein product of sna contains five copies of a nucleic acid-binding finger motif previously identified in two transcription factors, and in the protein product of several putative regulatory genes.

Amino Acid Sequence↗
PubMed1988

Two developmental genes encoding sigma factor homologs are arranged in tandem in Bacillus subtilis.

The sporulation-essential gene spoIIG of the Gram-positive bacterium Bacillus subtilis encodes the sporulation-specific sigma factor sigma 29(sigma E). We report here the initial characterization of a gene, referred to as ORF3, located immediately downstream of the spoIIG gene. The results indicate that ORF3 encodes a sigma homolog, whose expression is highly regulated during development. Analysis of the ORF3 nucleotide sequence reveals an open reading frame encoding a polypeptide of 260 amino acid residues (molecular mass of 30.1 kDa). Its predicted amino acid sequence shows significant similarity to that of other RNA polymerase sigma factor sequences. S1 nuclease mapping experiments indicate that ORF3 is initially cotranscribed with spoIIG from about 1 to 4 hr into the sporulation process and that later on ORF3 is transcribed independently from a new site located between spoIIG and ORF3. The role of ORF3 was investigated by constructing a deletion mutation in its structural gene. The mutant exhibits normal growth but is unable to produce heat-resistant spores. We propose that the ORF3 gene product is a sigma factor or a related peptide essential for sporulation at a late stage of development.

Amino Acid Sequence↗
PubMed1997

[Developmental genes and dysmorphology].

Until recently, clinical dysmorphology was the poor parent of clinical medicine and human genetics. However, the studies of children affected with multiple congenital abnormality syndromes are the first step to recognize syndromes for diagnosis identification, leading to prognosis and care for the children and to genetic counseling for the family. These studies must lead to the identification and analysis of developmental genes involved in normal and abnormal morphogenesis. Dysmorphology leads to a better understanding of abnormal development, genetic causes and embryological development. The identification of different genes from various gene families involved in dysmorphogenesis has recently emerged. These developmental genes often act as patterning genes and as possible oncogenes; they are of interest for developmental biologists and for medical geneticists.

Abnormalities, Multiple↗