scholarly journals Genetic imprinting of IGF2/H19 in Normal, Hyperplastic and Neoplastic Cells

1996 ◽  
Vol 45 (1-2) ◽  
pp. 91-92
Author(s):  
R. Ohlsson ◽  
T.J. Ekström ◽  
G. Adam ◽  
S. Miller ◽  
H. Cui ◽  
...  

Genetic imprinting implies the preferential or exclusive expression of one of the parental alleles of a subset of autosomal loci. The insulin-like growth factor II (IGF2) and H19 loci are particularly interesting examples of this phenomenon since their products appear to display growth agonistic and antagonistic properties, respectively. In addition, IGF2 and H19 are only 90 kb apart, are expressed from opposite parental alleles [1,2] and show a striking similarity in their spatial expression patterns during human prenatal development [3]. One exception is the choroid plexus and leptomeninges which express 1GF2 biallically with no detectable H19 expression [3]. Observations like these have fuelled ideas that there is an enhancer competition between the IGF2 and H19 loci [4]. The imprinting status of the H19 locus would then indirectly control the expressivity of IGF2. This model is likely to be too simple since the P1 promoter of IGF2 is not functionally imprinted during liver development in humans [4]. Moreover, while the liver P2-P4 promoters are expressed primarily from the paternally derived allele during human prenatal development, the P2-P4 promoters can be expressed from both parental alleles in complex patterns during postnatal human development [5]. The enhancer competition model might be put to the test in human and mouse uniparental embryos since the parental origin of their diploid genomes cannot be discerned. Unexpectedly, H19 which is expressed preferentially from the maternal allele in mouse [6] and human [7] placenta is expressed in both mouse and human trophoblasts (in complete hydatidiform moles) lacking the maternal genome. In the normal human placenta, the repressed paternal H19 allele is more methylated. Interestingly, the CpG methylation pattern of H19 is strikingly similar between normal placenta and complete moles. Hence, both paternal H19 alleles are similarly methylated indicating that postzygotic modification events typical of normal development have taken place in complete moles as well in spite of the absence of the maternal genome. In contrast to the normal placenta, H19 is expressed biallelically in complete moles as assessed by allele-specific in situ hybridisation analysis of dispermie moles [8]. We discuss these results in relation to current models of IGF2/H19 imprinting mechanism(s).

Author(s):  
Ruben Plöger ◽  
Christoph Viebahn

AbstractThe anterior-posterior axis is a central element of the body plan and, during amniote gastrulation, forms through several transient domains with specific morphogenetic activities. In the chick, experimentally proven activity of signalling molecules and transcription factors lead to the concept of a ‘global positioning system’ for initial axis formation whereas in the (mammotypical) rabbit embryo, a series of morphological or molecular domains are part of a putative ‘three-anchor-point model’. Because circular expression patterns of genes involved in axis formation exist in both amniote groups prior to, and during, gastrulation and may thus be suited to reconcile these models, the expression patterns of selected genes known in the chick, namely the ones coding for the transcription factors eomes and tbx6, the signalling molecule wnt3 and the wnt inhibitor pkdcc, were analysed in the rabbit embryonic disc using in situ hybridisation and placing emphasis on their germ layer location. Peripheral wnt3 and eomes expression in all layers is found initially to be complementary to central pkdcc expression in the hypoblast during early axis formation. Pkdcc then appears — together with a posterior-anterior gradient in wnt3 and eomes domains — in the epiblast posteriorly before the emerging primitive streak is marked by pkdcc and tbx6 at its anterior and posterior extremities, respectively. Conserved circular expression patterns deduced from some of this data may point to shared mechanisms in amniote axis formation while the reshaping of localised gene expression patterns is discussed as part of the ‘three-anchor-point model’ for establishing the mammalian body plan.


2006 ◽  
Vol 235 (2) ◽  
pp. 468-477 ◽  
Author(s):  
Shigehito Yamada ◽  
Chigako Uwabe ◽  
Tomoko Nakatsu-Komatsu ◽  
Yutaka Minekura ◽  
Masaji Iwakura ◽  
...  

2021 ◽  
Author(s):  
Csaba Kerepesi ◽  
Bohan Zhang ◽  
Sang-Goo Lee ◽  
Alexandre Trapp ◽  
Vadim N. Gladyshev

The notion that germline cells do not age goes back to the 19th century ideas of August Weismann. However, being in a metabolically active state, they accumulate damage and other age-related changes over time, i.e., they age. For new life to begin in the same young state, they must be rejuvenated in the offspring. Here, we developed a new multi-tissue epigenetic clock and applied it, together with other aging clocks, to track changes in biological age during mouse and human prenatal development. This analysis revealed a significant decrease in biological age, i.e. rejuvenation, during early stages of embryogenesis, followed by an increase in later stages. We further found that pluripotent stem cells do not age even after extensive passaging and that the examined epigenetic age dynamics is conserved across species. Overall, this study uncovers a natural rejuvenation event during embryogenesis and suggests that the minimal biological age (the ground zero) marks the beginning of organismal aging.


2021 ◽  
Vol 15 ◽  
Author(s):  
Chao Fang ◽  
Hong Wang ◽  
Robert Konrad Naumann

The claustrum is an enigmatic brain structure thought to be important for conscious sensations. Recent studies have focused on gene expression patterns, connectivity, and function of the claustrum, but relatively little is known about its development. Interestingly, claustrum-enriched genes, including the previously identified marker Nurr1, are not only expressed in the classical claustrum complex, but also embedded within lateral neocortical regions in rodents. Recent studies suggest that Nurr1 positive neurons in the lateral cortex share a highly conserved genetic expression pattern with claustrum neurons. Thus, we focus on the developmental progression and birth dating pattern of the claustrum and Nurr1 positive neurons in the lateral cortex. We comprehensively investigate the expression of Nurr1 at various stages of development in the rat and find that Nurr1 expression first appears as an elongated line along the anterior-posterior axis on embryonic day 13.5 (E13.5) and then gradually differentiates into multiple sub-regions during prenatal development. Previous birth dating studies of the claustrum have led to conflicting results, therefore, we combine 5-ethynyl-2′-deoxyuridine (EdU) labeling with in situ hybridization for Nurr1 to study birth dating patterns. We find that most dorsal endopiriform (DEn) neurons are born on E13.5 to E14.5. Ventral claustrum (vCL) and dorsal claustrum (dCL) are mainly born on E14.5 to E15.5. Nurr1 positive cortical deep layer neurons (dLn) and superficial layer neurons (sLn) are mainly born on E14.5 to E15.5 and E15.5 to E17.5, respectively. Finally, we identify ventral to dorsal and posterior to anterior neurogenetic gradients within vCL and DEn. Thus, our findings suggest that claustrum and Nurr1 positive neurons in the lateral cortex are born sequentially over several days of embryonic development and contribute toward charting the complex developmental pattern of the claustrum in rodents.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Nicole Gross ◽  
Maria Giuseppina Strillacci ◽  
Francisco Peñagaricano ◽  
Hasan Khatib

AbstractEmbryos utilize oocyte-donated RNAs until they become capable of producing RNAs through embryonic genome activation (EGA). The sperm’s influence over pre-EGA RNA content of embryos remains unknown. Recent studies have revealed that sperm donate non-genomic components upon fertilization. Thus, sperm may also contribute to RNA presence in pre-EGA embryos. The first objective of this study was to investigate whether male fertility status is associated with the RNAs present in the bovine embryo prior to EGA. A total of 65 RNAs were found to be differentially expressed between 2–4 cell bovine embryos derived from high and low fertility sires. Expression patterns were confirmed for protein phosphatase 1 regulatory subunit 36 (PPP1R36) and ataxin 2 like (ATXN2L) in three new biological replicates. The knockdown of ATXN2L led to a 22.9% increase in blastocyst development. The second objective of this study was to characterize the parental origin of RNAs present in pre-EGA embryos. Results revealed 472 sperm-derived RNAs, 2575 oocyte-derived RNAs, 2675 RNAs derived from both sperm and oocytes, and 663 embryo-exclusive RNAs. This study uncovers an association of male fertility with developmentally impactful RNAs in 2–4 cell embryos. This study also provides an initial characterization of paternally-contributed RNAs to pre-EGA embryos. Furthermore, a subset of 2–4 cell embryo-specific RNAs was identified.


2015 ◽  
Vol 27 (1) ◽  
pp. 141 ◽  
Author(s):  
R. Xiang ◽  
C. A. S. Estrella ◽  
C. J. Fitzsimmons ◽  
Z. A. Kruk ◽  
D. A. Thomsen ◽  
...  

The placenta, a major determinant of fetal growth in eutherians, facilitates maternal-fetal cross talk and mediates programming of postnatal phenotype via genetic and epigenetic mechanisms. However, magnitude and specificity of effects of maternal and paternal genomes on placental and fetal phenotype and their relationships are unclear. Using an outbred bovine intra-species model with well-defined Bos taurus taurus and Bos taurus indicus maternal and paternal genetics, we generated purebred and reciprocal cross fetuses (Animal Ethics No. S-094-2005) to dissect and quantify effects of parental genomes, fetal sex, and nongenetic maternal effects (maternal weight and post-conception maternal weight gain) on 41 gross and histomorphological feto-placental parameters. Analysis of data from 73 fetuses recovered at midgestation (Day 153) with general linear models (Xiang et al. 2014 JBMR http://dx.doi.org/10.1002/jbmr.2263) using the GLM procedure of R version 22.14 (R Development Core Team, Vienna, Austria) revealed that maternal and paternal genome combined explained the highest proportion of variation (47.2–99.5%) in 30 investigated parameters with significant (P < 0.05–0.0001) models. Fetal sex accounted for up to 32.2% (P < 0.05–0.0001) and nongenetic maternal effects for up to 25.1% (P < 0.05–0.001) of variation in 11 and 14 parameters, respectively. Partitioning of parental (epi)genome variation showed that the maternal genome predominantly contributed to variation in gross (80.3–95.7%; P < 0.05–0.0001) and histomorphological (51.5–82.1%; P < 0.05–0.0001) placental parameters, fetal weight (54.1%; P < 0.0001), and fetal organ weights (43.7–73.1%; P < 0.05–0.0001), whereas the paternal genome predominantly contributed to fetal fluids weight (73.0%; P < 0.001), umbilical cord weight (73.9%; P < 0.05) and length (73.2%; P < 0.01), and placental (69.6%; P < 0.05) and umbilical cord (83.2%; P < 0.0001) efficiency. Our finding that the maternal genome determined placental phenotype (i.e. nutrient source) and the paternal genome determined umbilical cord and fetal fluid phenotype (i.e. nutrient flow) is in line with predicted expression patterns of genomic imprinting effects by both maternal-offspring coadaptation (Wolf and Hager 2006 PLoS Biol. 4, e380) and conflict-of-interest (Moore and Haig 1991 Trends Genet 7, 45–49) hypotheses in the feto-placental unit. Furthermore, there were 4 maternal genome determined relationships between placental weights and umbilical cord phenotype (P < 0.05–0.0001) and 28 paternal genome and/or fetal sex-determined relationships between fetus-, organ- and fetal fluid weights and umbilical cord phenotype (P < 0.05–0.0001). The finding of specific relationships between placenta and fetus merging in clusters differentiated by maternal and paternal genome effects suggests the existence of (epi)genetic-regulated morphological modules within the feto-placental unit.Funded by the JS Davies Bequest.


2000 ◽  
Vol 278 (5) ◽  
pp. R1305-R1313 ◽  
Author(s):  
Yvonne H. J. M. Arens ◽  
Charles R. Rosenfeld ◽  
Kristine E. Kamm

Maturation rates of vascular and visceral smooth muscle (SM) during ovine development were compared by quantifying contractile protein, myosin heavy chain (MHC) isoform contents, and contractile properties of aortas and bladders from female fetal ( n = 19) and postnatal ( n = 21) sheep. Actin, myosin, and protein contents rose progressively throughout development in both tissues ( P ≤ 0.003); however, expression patterns differed. During the last trimester, i.e., 101–130 days (term ∼145 days), bladder actin and MHC contents were approximately twofold greater ( P < 0.04) than those in the aorta. Although the fractional content of 204-kDa SM1 MHC in the bladder decreased from 74 ± 3% at midgestation to 48 ± 2% 3 mo postnatal, the aorta exhibited an increase from 30 ± 2% to 65 ± 2%. Bladder MHC (MHC-B) migrating at 200 kDa contained only SM2 throughout development. In contrast, 200-kDa MHC in the aorta was predominantly nonmuscle MHC-B at midgestation, which was gradually replaced by SM2 as development progressed. Along with its early expression of SM2, bladder muscle obtained maximal stress generating capacity (1.7 × 105 N/m2) by term gestation, whereas the aorta exhibited no contractions until after birth. We conclude that whereas aortic SM maturation is delayed until after birth, bladder SM matures biochemically and functionally during prenatal development, thus supporting early requirements for micturition.


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