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PubMed1983

Drosophila has one myosin heavy-chain gene with three developmentally regulated transcripts.

We have isolated overlapping genomic clones that contain a single-copy myosin heavy-chain gene of Drosophila melanogaster. By the criteria of hybridization under nonstringent conditions, this is the only myosin heavy-chain gene of the fly. The gene is localized to the chromosomal region 36B. The transcriptional unit has a length of about 19 kb and contains at least nine introns. There are three mature mRNA species expressed from the gene, with molecular lengths of 7.2 kb, 8.0 kb and 8.6 kb. The former two are expressed abundantly during those stages of development when larval muscle proteins are being synthesized; the latter two are expressed when the principal muscle proteins of the adult are made. The three transcripts differ primarily in their respective patterns of splicing at the 3' ends.

Animals↗
PubMed1993

Alternative splicing of Pax-8 gene transcripts is developmentally regulated and generates isoforms with different transactivation properties.

Pax-8, a member of the paired box-containing gene family, was shown to be coexpressed with Pax-2 in several human kidney carcinoma cell lines. Four different Pax-8 mRNA isoforms, a to d, were cloned from one of these cell lines by polymerase chain reaction amplification, and the Pax-8 gene was isolated from a human cosmid library. Analysis of the exon-intron structure of Pax-8 revealed that the four mRNA isoforms arise by alternative splicing, resulting in inclusion or exclusion of exon 7 and/or exon 8 sequences. All four Pax-8 proteins retain the paired domain as their DNA-binding motif and recognize DNA in the same manner as do the closely related Pax-2 and BSAP (Pax-5) proteins. The Pax-8a and Pax-8b isoforms end in a serine/threonine/tyrosine-rich sequence, while the C terminus of Pax-8c and Pax-8d is translated in a different, proline-rich reading frame. Transient transfection experiments revealed that Pax-8 isoforms a and b, but not c and d, strongly stimulate transcription from a promoter containing six copies of a paired-domain recognition sequence. The same four mRNA variants were also detected by RNase protection analysis in the mouse embryo and adult kidney, thus indicating evolutionary conservation of Pax-8 mRNA splicing. A different splice pattern was observed in the developing placenta, which expresses two new variants, Pax-8e and Pax-8f, instead of transcripts b to d. Expression of these mRNAs is high at embryonic day 9.5 and is gradually reduced until Pax-8a is the predominant transcript in the 12.5-day placenta. In the embryo, however, the synthesis of mRNAs b to d is initially low and then increases relative to that of Pax-8a. Hence, alternative splicing of Pax-8 gene transcripts not only generates six different Pax-8 variants but is also temporally and spatially regulated during early mouse development.

Alternative Splicing↗
PubMed1992

Developmental regulation of globin gene expression.

We have used the globin family of genes in chicken to study developmental regulation of gene expression, both at the level of individual interaction of trans-acting factors with local promoters and enhancers, and at the level of chromatin structure. Regulation of all members of the alpha- and beta-globin clusters is affected by the erythroid regulatory factor GATA-1. Separate mechanisms exist for regulation of individual members of the family. As an example, we describe the control mechanisms that play a role in the expression of the rho-globin gene, which is expressed only in primitive lineage erythroid cells. In addressing the involvement of chromatin structure in gene activation, we have examined the role of locus control elements, and also considered the way in which RNA polymerase molecules might accommodate to the presence of nucleosomes on transcribed genes.

Animals↗
PubMed2005

The neuronal ceroid lipofuscinosis Cln8 gene expression is developmentally regulated in mouse brain and up-regulated in the hippocampal kindling model of epilepsy.

BACKGROUND: The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by accumulation of autofluorescent material in many tissues, especially in neurons. Mutations in the CLN8 gene, encoding an endoplasmic reticulum (ER) transmembrane protein of unknown function, underlie NCL phenotypes in humans and mice. The human phenotype is characterized by epilepsy, progressive psychomotor deterioration and visual loss, while motor neuron degeneration (mnd) mice with a Cln8 mutation show progressive motor neuron dysfunction and retinal degeneration. RESULTS: We investigated spatial and temporal expression of Cln8 messenger ribonucleic acid (mRNA) using in situ hybridization, reverse transcriptase polymerase chain reaction (RT-PCR) and northern blotting. Cln8 is ubiquitously expressed at low levels in embryonic and adult tissues. In prenatal embryos Cln8 is most prominently expressed in the developing gastrointestinal tract, dorsal root ganglia (DRG) and brain. In postnatal brain the highest expression is in the cortex and hippocampus. Expression of Cln8 mRNA in the central nervous system (CNS) was also analyzed in the hippocampal electrical kindling model of epilepsy, in which Cln8 expression was rapidly up-regulated in hippocampal pyramidal and granular neurons. CONCLUSION: Expression of Cln8 in the developing and mature brain suggests roles for Cln8 in maturation, differentiation and supporting the survival of different neuronal populations. The relevance of Cln8 up-regulation in hippocampal neurons of kindled mice should be further explored.

Animals↗
PubMed1994

A behavioral neurogenetics approach to developmental disabilities: gene-brain-behavior associations.

This review provides a discussion of behavioral neurogenetics' contribution to understanding neurodevelopmental pathways in learning and developmental disabilities. A brief overview is given of several common neurogenetic disorders with various genetic etiologies including Down syndrome, Turner syndrome, Prader-Willi syndrome, Angelman syndrome, and Tourette's syndrome. Special emphasis is placed on fragile X syndrome as representative of a newly-discovered class of genetic conditions characterized by an unstable trinucleotide repeat. A spectrum of cognitive, behavioral, and social-emotional phenotypic features associated with fragile X syndrome is examined. Also included are findings from recent neuroimaging research and a discussion of the need for the classification of symptoms on the basis of underlying genetic/medical conditions.

Adult↗
PubMed2005

The new look of behavioral genetics in developmental psychopathology: gene-environment interplay in antisocial behaviors.

This article reviews behavioral-genetic research to show how it can help address questions of causation in developmental psychopathology. The article focuses on studies of antisocial behavior, because these have been leading the way in investigating environmental as well as genetic influences on psychopathology. First, the article illustrates how behavioral-genetic methods are being newly applied to detect the best candidates for genuine environmental causes among the many risk factors for antisocial behavior. Second, the article examines findings of interaction between genes and environments (G x E) associated with antisocial behavior, outlining steps for testing hypotheses of measured G x E. Third, the article envisages future work on gene-environment interplay, arguing that it is an interesting and profitable way forward for psychopathology research.

Antisocial Personality Disorder↗
PubMed2005

T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer.

The ribonuclease III enzyme Dicer is essential for the processing of micro-RNAs (miRNAs) and small interfering RNAs (siRNAs) from double-stranded RNA precursors. miRNAs and siRNAs regulate chromatin structure, gene transcription, mRNA stability, and translation in a wide range of organisms. To provide a model system to explore the role of Dicer-generated RNAs in the differentiation of mammalian cells in vivo, we have generated a conditional Dicer allele. Deletion of Dicer at an early stage of T cell development compromised the survival of alphabeta lineage cells, whereas the numbers of gammadelta-expressing thymocytes were not affected. In developing thymocytes, Dicer was not required for the maintenance of transcriptional silencing at pericentromeric satellite sequences (constitutive heterochromatin), the maintenance of DNA methylation and X chromosome inactivation in female cells (facultative heterochromatin), and the stable shutdown of a developmentally regulated gene (developmentally regulated gene silencing). Most remarkably, given that one third of mammalian mRNAs are putative miRNA targets, Dicer seems to be dispensable for CD4/8 lineage commitment, a process in which epigenetic regulation of lineage choice has been well documented. Thus, although Dicer seems to be critical for the development of the early embryo, it may have limited impact on the implementation of some lineage-specific gene expression programs.

Animals↗
PubMed1995

PAX genes: what's new in developmental biology and cancer?

PAX genes encode nuclear transcription factors which are rapidly becoming regarded as major controllers of developmental processes in both vertebrates and invertebrates. Mutations in murine Pax genes underlie three natural mouse alleles and two corresponding human syndromes. Murine Pax genes have been shown to be proto-oncogenes. Furthermore, human PAX genes have recently been demonstrated to play an influential part in some common human cancers. The diversity in effects of PAX genes reflects that of their structure. All encode a DNA-binding domain termed the paired domain and in addition some also encode a second binding domain--the paired type homeobox.

Animals↗
PubMed2004

A genome-wide study of gene activity reveals developmental signaling pathways in the preimplantation mouse embryo.

The preimplantation development of the mammalian embryo encompasses a series of critical events: the transition from oocyte to embryo, the first cell divisions, the establishment of cellular contacts, the first lineage differentiation-all the first subtle steps toward a future body plan. Here, we use microarrays to explore gene activity during preimplantation development. We reveal robust and dynamic patterns of stage-specific gene activity that fall into two major phases, one up to the 2-cell stage (oocyte-to-embryo transition) and one after the 4-cell stage (cellular differentiation). The mouse oocyte and early embryo express components of multiple signaling pathways including those downstream of Wnt, BMP, and Notch, indicating that conserved regulators of cell fate and pattern formation are likely to function at the earliest embryonic stages. Overall, these data provide a detailed temporal profile of gene expression that reveals the richness of signaling processes in early mammalian development.

Animals↗
PubMed2004

Amphibian cardiac troponin I gene's organization, developmental expression, and regulatory properties are different from its mammalian homologue.

In mammals, the expression of the troponin I-slow (TnIs) isoform is predominant in the heart during embryogenesis and, shortly after birth, is replaced by the cardiac-specific isoform, TnIc; a developmental switch thought to be mediated by thyroid hormone. Whereas, in Xenopus, TnIc is expressed at the onset of heart formation and is the only TnI isoform expressed in the heart. Herein, we demonstrate that the expression patterns of these genes appear to be common within the anuran lineage and, unlike their mammalian counterparts, are not affected by thyroid hormone. To elucidate the regulatory mechanism(s) governing the expression of the amphibian TnIc gene, we characterized the TnIc gene from Rana catesbeiana and used its 5'-flanking region to drive expression of green fluorescent protein in the Xenopus transgenic system. Our results demonstrate that a 300-bp minimal promoter containing intact GATA and CArG-box elements is sufficient to drive expression of this reporter gene in a pattern that mimics, both spatially and temporally, the expression of the endogenous Xenopus TnIc gene.

Amino Acid Sequence↗
PubMed2000

Developmentally regulated, alternative splicing of the Rpn10 gene generates multiple forms of 26S proteasomes.

The 26S proteasome is a multisubunit protein- destroying machinery that degrades ubiquitin-tagged proteins. To date only a single species of Rpn10, which possibly functions as a multiubiquitin chain-binding subunit, has been identified in various organisms. Here we report that mouse Rpn10 mRNAs occur in at least five distinct forms, named Rpn10a to Rpn10e, and that they are generated from a single gene by developmentally regulated, alternative splicing. Rpn10a is ubiquitously expressed, whereas Rpn10e is expressed only in embryos, with the highest levels of expression in the brain. Both forms of Rpn10 are components of the 26S proteasome, with an apparently similar affinity for multiubiquitylated [(125)I]lysozyme in vitro. However, they exert markedly divergent effects on the destruction of B-type cyclin in Xenopus egg extracts. Thus, the 26S proteasome occurs in at least two functionally distinct forms: one containing a ubiquitously expressed Rpn10a and the other a newly identified, embryo-specific Rpn10e. While the former is thought to perform proteolysis constitutively in a wide variety of cells, the latter may play a specialized role in early embryonic development.

Alternative Splicing↗
PubMed1994

Anabaena xisF gene encodes a developmentally regulated site-specific recombinase.

Two DNA elements are excised from the chromosome during Anabaena heterocyst differentiation. We have identified the gene xisF which encodes the site-specific recombinase responsible for the excision of a 55-kb element from within the fdxN gene. The cloned xisF gene is sufficient to cause site-specific rearrangement of an artificial substrate in Escherichia coli. Inactivation of xisF in the Anabaena chromosome prevents excision of the fdxN element and growth in nitrogen-deficient medium but does not alter the development of heterocysts. Forced transcription of xisF in vegetative cells did not result in excision of the fdxN element, suggesting that other factors may be involved in cell-type specificity. The predicted XisF protein shows significant similarity to the Bacillus subtilis SpoIVCA recombinase.

Amino Acid Sequence↗
PubMed1991

The secretin gene: evolutionary history, alternative splicing, and developmental regulation.

The gene encoding the hormone secretin has been isolated and structurally characterized. The transcriptional unit is divided into four exons spanning 813 nucleotides. Comparison of the rat secretin gene to the other members of the glucagon-secretin gene family reveals that similarities are restricted to the exons encoding the biologically active peptides. Analysis of RNA from porcine intestine indicates that at least two transcripts are generated from the porcine secretin gene as a result of differential splicing. The longer and more abundant transcript appears to be identical to a previously isolated cDNA, which encodes a precursor that includes a 72-amino acid C-terminal extension peptide. The shorter transcript does not contain the third exon and, as a result, encodes only 44 residues beyond the C terminus of secretin. The amino acid sequence deduced from the shorter transcript is identical to a precursor form of secretin recently isolated from porcine duodenum [Gafvelin, G., Jornvall, H. & Mutt, V. (1990) Proc. Natl. Acad. Sci. USA 87, 6781-6785]. Developmental studies reveal that both secretin mRNA and peptide levels in the intestine are highest just before birth, prior to the onset of gastric acid secretion and feeding. This observation implies that secretin biosynthesis in developing animals is controlled independently of the principal factors known to regulate secretin release in adult animals.

Amino Acid Sequence↗
PubMed1994

Extracellular cAMP can restore development in Dictyostelium cells lacking one, but not two subtypes of early cAMP receptors (cARs). Evidence for involvement of cAR1 in aggregative gene expression.

Extracellular cAMP induces expression of several classes of developmentally regulated genes in Dictyostelium. Four highly homologous surface cAMP receptors (cARs) were identified earlier, but involvement of specific cARs in gene regulation has not been clarified. Cells lacking the chemotactic receptor, cAR1, neither aggregate nor express developmentally regulated genes. Expression of aggregative genes is in wild-type cells induced by nanomolar cAMP pulses and repressed by persistent micromolar cAMP stimuli, which induce expression of prespore and prestalk-enriched genes during the postaggregative stages of development. We show here that in cell lines carrying a cAR1 gene disruption, nanomolar pulses cannot induce aggregative gene expression. Remarkably, micromolar cAMP can induce expression of aggregative genes in car1- cells as well as expression of prespore and prestalk-enriched genes, and furthermore restores their ability to form normal slugs and fruiting bodies. These data indicate that cAR1 mediates aggregative but not postaggregative gene expression and morphogenesis, and suggest that after gene disruption, its function is partially taken over by a lower affinity receptor that is not subjected to desensitization. The absence of another early cAMP receptor, cAR3, does not affect development. However, in a car1-/car3- double mutant, cAMP stimulation cannot restore any developmental gene expression, indicating that cAR3 may have substituted for cAR1 in car1- cell lines.

Animals↗
PubMed1989

Bicaudal-D, a Drosophila gene involved in developmental asymmetry: localized transcript accumulation in ovaries and sequence similarity to myosin heavy chain tail domains.

The Bicaudal-D (Bic-D) gene is essential for the differentiation of the oocyte in Drosophila. Dominant gain-of-function mutations result in the formation of double abdomen embryos. The Bic-D gene was cloned and identified using restriction fragment length polymorphisms, Northern analysis, and transformation rescue. Bic-D RNA accumulates in the oocyte during the earliest stages of oogenesis and is localized anteriorly in later stages. The predicted protein contains several extended amphipathic helices, and its similarity to myosin heavy chain tails, paramyosin, and kinesin suggests a similar type of coiled-coil protein interaction.

Amino Acid Sequence↗
PubMed1999

Dictyostelium ribosomal protein genes and the elongation factor 1B gene show coordinate developmental regulation which is under post-transcriptional control.

Starvation for amino acids initiates the developmental program in the cellular slime mold, Dictyostelium discoideum [19, 20]. One of the earliest developmental events is the decline in ribosomal protein synthesis [2, 17, 29, 30]. The ribosomal protein mRNAs are excluded from polysomes with 20 min to 1 h following the removal of nutrients, and their mRNA levels decline sharply at about 9 h into the 24-h developmental cycle [28, 31, 35, 36]. It has been generally assumed that the decline in r-protein mRNA levels during late development reflected a decline in the transcription rate [12, 32, 43]. Here we demonstrate that this is not the case. The transcription rates of three ribosomal protein genes, rpL11, rpL23 and rpS9 as well as an elongation factor 1B gene have been determined during growth and development in Dictyostelium. Throughout growth and development the transcription rate of the ribosomal protein genes remains relatively constant at 0.2%-0.5% of the rate of rRNA transcription while the elongation factor 1B gene is transcribed at 0.4%-0.6% of the rRNA rate. This low but constant transcription rate is in contrast to a spore coat protein gene Psp D, which is transcribed at 6% of the rRNA rate in late developing cells. The elongation factor 1B gene appears to be co-regulated with the ribosomal protein genes both in terms of its transcription rate and mRNA accumulation. Dictyostelium has been a popular model for understanding signal transduction and the growth to differentiation transition, thus it is of significance that the regulation of ribosome biosynthesis in Dictyostelium resembles that of higher eukaryotes in being regulated largely at the post-transcriptional level in response to starvation as opposed to yeasts where the regulation is largely transcriptional [27].

Amino Acid Sequence↗
PubMed2005

Effect of culture environment on gene expression and developmental characteristics in IVF-derived embryos.

It is generally accepted that mammalian preimplantation embryos are sensitive to their environment and that conditions of culture can affect future growth and developmental potential both pre- and postnatally. Evidence suggests that while culture conditions during bovine in vitro embryo production can impact somewhat on the developmental potential of the early embryo, the intrinsic quality of the oocyte is the key factor determining the proportion of oocytes developing to the blastocyst stage. In addition, evidence suggests that the period of post fertilization embryo culture is the most critical period affecting blastocyst quality assessed in terms of cryotolerance, gene expression pattern and ability to establish a pregnancy. This paper reviews the current literature, with emphasis on the bovine model, demonstrating evidence for an effect of post fertilization culture environment on embryo gene expression and quality.

Animals↗