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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↗
PubMed2005

Developmental gene amplification: insights into DNA replication and gene expression.

In the formation of a complex organism and the differentiation of specific cell types, there are often demands for high levels of particular gene products. These demands can be met by increasing transcription or translation, or by decreasing the rate of mRNA or protein turnover. Although these are the most common means to increase expression levels, there is another mechanism: gene amplification. Developmental gene amplification is a DNA replication-based process whereby specific genes are replicated above the copy number of surrounding sequences, resulting in an increase in the template available for transcription. Recent microarray studies in Drosophila melanogaster have identified two additional amplicons, suggesting that developmental gene amplification might be more widely used than was previously thought. Furthermore, work in both Drosophila and the related fly, Sciara coprophila, has yielded insights into the mechanisms, regulatory sequences and proteins controlling DNA replication during gene amplification, including a link between transcription factors and origin usage.

Animals↗
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↗
PubMed2000

Identification and characterization of genes required for early Myxococcus xanthus developmental gene expression.

Starvation and cell density regulate the developmental expression of Myxococcus xanthus gene 4521. Three classes of mutants allow expression of this developmental gene during growth on nutrient agar, such that colonies of strains containing a Tn5 lac Omega4521 fusion are Lac(+). One class of these mutants inactivates SasN, a negative regulator of 4521 expression; another class activates SasS, a sensor kinase-positive regulator of 4521 expression; and a third class blocks lipopolysaccharide (LPS) O-antigen biosynthesis. To identify additional positive regulators of 4521 expression, 11 Lac(-) TnV. AS transposon insertion mutants were isolated from a screen of 18,000 Lac(+) LPS O-antigen mutants containing Tn5 lac Omega4521 (Tc(r)). Ten mutations identified genes that could encode positive regulators of 4521 developmental expression based on their ability to abolish 4521 expression during development in the absence of LPS O antigen and in an otherwise wild-type background. Eight of these mutations mapped to the sasB locus, which encodes the known 4521 regulators SasS and SasN. One mapped to sasS, whereas seven identified new genes. Three mutations mapped to a gene encoding an NtrC-like response regulator homologue, designated sasR, and four others mapped to a gene designated sasP. One mutation, designated ssp10, specifically suppressed the LPS O-antigen defect; the ssp10 mutation had no effect on 4521 expression in an otherwise wild-type background but reduced 4521 developmental expression in the absence of LPS O antigen to a level close to that of the parent strain. All of the mutations except those in sasP conferred defects during growth and development. These data indicate that a number of elements are required for 4521 developmental expression and that most of these are necessary for normal growth and fruiting body development.

Bacterial Proteins↗
PubMed2006

A bivalent chromatin structure marks key developmental genes in embryonic stem cells.

The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development. We explored this by examining histone methylation in mouse embryonic stem (ES) cells across 56 large HCNE-rich loci. We identified a specific modification pattern, termed "bivalent domains," consisting of large regions of H3 lysine 27 methylation harboring smaller regions of H3 lysine 4 methylation. Bivalent domains tend to coincide with TF genes expressed at low levels. We propose that bivalent domains silence developmental genes in ES cells while keeping them poised for activation. We also found striking correspondences between genome sequence and histone methylation in ES cells, which become notably weaker in differentiated cells. These results highlight the importance of DNA sequence in defining the initial epigenetic landscape and suggest a novel chromatin-based mechanism for maintaining pluripotency.

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↗
PubMed2006

Patterns of conservation and change in honey bee developmental genes.

The current insect genome sequencing projects provide an opportunity to extend studies of the evolution of developmental genes and pathways in insects. In this paper we examine the conservation and divergence of genes and developmental processes between Drosophila and the honey bee; two holometabolous insects whose lineages separated approximately 300 million years ago, by comparing the presence or absence of 308 Drosophila developmental genes in the honey bee. Through examination of the presence or absence of genes involved in conserved pathways (cell signaling, axis formation, segmentation and homeobox transcription factors), we find that the vast majority of genes are conserved. Some genes involved in these processes are, however, missing in the honey bee. We have also examined the orthology of Drosophila genes involved in processes that differ between the honey bee and Drosophila. Many of these genes are preserved in the honey bee despite the process in which they act in Drosophila being different or absent in the honey bee. Many of the missing genes in both situations appear to have arisen recently in the Drosophila lineage, have single known functions in Drosophila, and act early in developmental pathways, while those that are preserved have pleiotropic functions. An evolutionary interpretation of these data is that either genes with multiple functions in a common ancestor are more likely to be preserved in both insect lineages, or genes that are preserved throughout evolution are more likely to co-opt additional functions.

Amino Acid Sequence↗
PubMed2002

The systemin precursor gene regulates both defensive and developmental genes in Solanum tuberosum.

Transformation of Solanum tuberosum, cv. Desiree, with the tomato prosystemin gene, regulated by the 35S cauliflower mosaic virus promoter, resulted in constitutive increase in defensive proteins in potato leaves, similar to its effects in tomato plants, but also resulted in a dramatic increase in storage protein levels in potato tubers. Tubers from selected transformed lines contained 4- to 5-fold increases in proteinase inhibitor I and II proteins, >50% more soluble and dry weight protein, and >50% more total nitrogen and total free amino acids than found in wild-type tubers. These results suggest that the prosystemin gene plays a dual role in potato plants in regulating proteinase inhibitor synthesis in leaves in response to wounding and in regulating storage protein synthesis in potato tubers in response to developmental cues. The results indicated that components of the systemin signaling pathway normally found in leaves have been recruited by potato plants to be developmentally regulated to synthesize and accumulate large quantities of storage proteins in tubers.

Agrobacterium tumefaciens↗
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↗
PubMed2001

Isolation of novel developmental genes from human germ cell, oocyte and embryo cDNA by differential display.

Due to the difficulties inherent in research on human embryos, almost nothing is known about genes active in human early development. Although the human genome project will provide resources that theoretically provide access to every human gene, those genes specific to human early development may be difficult to define. Also, by definition, genes specific to early development will not be represented in cDNA databases derived from human somatic cells. Yet these unknown human developmental genes are likely to be of key importance for several areas of human health, including assisted reproduction and contraception, embryo stem cell research and tissue transplantation, ageing and cancer. In order to identify and isolate these human developmental genes, we have prepared amplified cDNA from human primordial germ cells, oocytes and embryos, and used differential display to compare patterns of gene expression in these embryonic cells and in the cells of somatic tissues of a 10-week human fetus. This paper reviews the highly sensitive procedures used to create amplified cDNA representing expressed genes in a single cell and the use of differential display to identify developmental genes. Several such genes have been isolated, but their full-length sequences and function are yet to be elucidated. Genes active in human early development are expected to play key roles in the maintenance of the archetypal stem cell state, potential immortality and the invasiveness of trophectoderm and primordial germ cells. They represent candidate genes regulating these functions for targeting in clinical research in human reproduction, stem cell differentiation and cancer.

Animals↗
PubMed2004

Developmental gene amplification and origin regulation.

Developmentally regulated gene amplification serves to increase the number of templates for transcription, yielding greatly increased protein and/or RNA product for gene(s) at the amplified loci. It is observed with genes that are very actively transcribed and during narrow windows of developmental time where copious amounts of those particular gene products are required. Amplification results from repeated firing of origins at a few genomic loci, while the rest of the genome either does not replicate, or replicates to a lesser extent. As such, amplification is a striking exception to the once-and-only-once rule of DNA replication and may be informative as to that mechanism. Drosophila amplifies eggshell (chorion) genes in the follicle cells of the ovary to allow for rapid eggshell synthesis. Sciara amplifies multiple genes in larval salivary gland cells that encode proteins secreted in the saliva for the pupal case. Finally, Tetrahymena amplifies its rRNA genes several thousand-fold in the creation of the transcriptionally active macronucleus. Due to the ease of molecular and genetic analysis with these systems, the study of origin regulation has advanced rapidly. Comparisons reveal an evolutionarily conserved trans-regulatory apparatus and a similar organization of sequence-specific cis-regulatory replicator and origin elements. The studies indicate a regulatory role for chromatin structure and transcriptionally active genes near the origins.

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↗