Expression of the insulin-like growth factor II gene in the choroid plexus and the leptomeninges of the adult rat central nervous system.

Stylianopoulou, Fotini; Herbert, Joseph; Soares, Marcelo B.; Efstratiadis, Argiris

doi:10.1073/pnas.85.1.141

Cited by 218 publications

(97 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results are consistent with the current notion of the regulation of Igf2, according to which increased methylation in DMR2 results in increased Igf2 expression. Consistent with previous studies, the levels of Igf2 transcript in frontal cortex of E17 embryos were too low to be assayed reliably (59,60).…”

Section: Igf2 Dmr2 and Dmd Methylation Status In E17 Frontalsupporting

confidence: 74%

Gestational Choline Deficiency Causes Global and Igf2 Gene DNA Hypermethylation by Up-regulation of Dnmt1 Expression

Kovacheva

Mellott

Davison

et al. 2007

Journal of Biological Chemistry

207

191

View full text Add to dashboard Cite

During gestation there is a high demand for the essential nutrient choline. Adult rats supplemented with choline during embryonic days (E) 11-17 have improved memory performance and do not exhibit age-related memory decline, whereas prenatally choline-deficient animals have memory deficits. Choline, via betaine, provides methyl groups for the production of S-adenosylmethionine, a substrate of DNA methyltransferases (DNMTs). We describe an apparently adaptive epigenomic response to varied gestational choline supply in rat fetal liver and brain. S-Adenosylmethionine levels increased in both organs of E17 fetuses whose mothers consumed a choline-supplemented diet. Surprisingly, global DNA methylation increased in choline-deficient animals, and this was accompanied by overexpression of Dnmt1 mRNA. Previous studies showed that the prenatal choline supply affects the expression of multiple genes, including insulin-like growth factor 2 (Igf2), whose expression is regulated in a DNA methylation-dependent manner. The differentially methylated region 2 of Igf2 was hypermethylated in the liver of E17 choline-deficient fetuses, and this as well as Igf2 mRNA levels correlated with the expression of Dnmt1 and with hypomethylation of a regulatory CpG within the Dnmt1 locus. Moreover, mRNA expression of brain and liver Dnmt3a and methyl CpG-binding domain 2 (Mbd2) protein as well as cerebral Dnmt3l was inversely correlated to the intake of choline. Thus, choline deficiency modulates fetal DNA methylation machinery in a complex fashion that includes hypomethylation of the regulatory CpGs within the Dnmt1 gene, leading to its overexpression and the resultant increased global and gene-specific (e.g. Igf2) DNA methylation. These epigenomic responses to gestational choline supply may initiate the long term developmental changes observed in rats exposed to varied choline intake in utero.An adequate supply of essential nutrients involved in the metabolism of methyl groups, including folic acid, vitamin B 12 , and choline, is central for normal development of the fetus. This is perhaps best exemplified by the discovery that the dietary supply of folic acid, a vitamin that acts as a coenzyme in one-carbon transfer pathways, during the periconceptual period is critical in prevention of neural tube defects (1). Studies in animal models (2-5) as well as recent epidemiological investigations in humans (6) indicate that choline intake during gestation is particularly important for the normal development and function of the central nervous system. In a frequently used experimental model that employs offspring of pregnant rats or mice consuming diets of varying choline content during the 7-day period of the second half of gestation (embryonic days E11-17), prenatal choline deficiency causes deficits in certain memory tasks (7), whereas prenatal choline supplementation leads to enhanced memory and attention and prevents agerelated memory decline (7-13). These behavioral changes are accompanied by electrophysiological, neuroanatomical, and neuro...

show abstract

Section: Igf2 Dmr2 and Dmd Methylation Status In E17 Frontalsupporting

confidence: 74%

Gestational Choline Deficiency Causes Global and Igf2 Gene DNA Hypermethylation by Up-regulation of Dnmt1 Expression

Kovacheva

Mellott

Davison

et al. 2007

Journal of Biological Chemistry

207

191

View full text Add to dashboard Cite

show abstract

“…During the first 3 weeks of postnatal life, Igf2 transcripts gradually decline to very low levels except in organs such as the brain, spinal cord, striated muscle and thymus. Within these organs, Igf2 transcripts and IGF-2 protein are also detected at adulthood [11,33,34,36,37]. In the present study, Igf2 transcripts and IGF-2 proteins were present both in adult and neonatal thymi from BBDR and WF rats.…”

Section: Discussionsupporting

confidence: 52%

Thymic expression of insulin-related genes in an animal model of autoimmune type 1 diabetes

Kecha-Kamoun

Achour

Martens

et al. 2001

Diabetes Metab. Res. Rev.

View full text Add to dashboard Cite

Background Insulin and multiple other autoantigens have been implicated in the pathogenesis of autoimmune type 1 diabetes, but the origin of immunological self-reactivity specifically oriented against insulin-secreting islet b-cells remains obscure. The primary objective of the present study was to investigate the hypothesis that a defect in thymic central T-cell selftolerance of the insulin hormone family could contribute to the pathophysiology of type 1 diabetes. This hypothesis was investigated in a classic animal model of type 1 diabetes, the Bio-Breeding (BB) rat.

show abstract

“…While the IGF proteins are also potent prenatal activators, it is mainly the IGF-II that acts prenatal (Rappolee et al, 1992;Stylianopoulou et al, 1988). However, neither IGF-I nor IGF-II, nor the receptors were greatly differentially regulated.…”

Section: Early Embryo Samplingmentioning

confidence: 99%

Transcriptome Expression Profiles in Prenatal Pigs in Relation to Myogenesis

Pas

Wit

Priem

et al. 2005

J Muscle Res Cell Motil

View full text Add to dashboard Cite

Myogenesis, the formation of muscle fibers, is a complex process. Pigs have been selected for efficient muscle growth for the past decades making them interesting to study myogenesis. We studied expression profiles of genes known to affect myogenesis, muscle structural proteins, and energy metabolism in prenatal pigs from 14 to 91 days of gestation. Primary and secondary muscle fiber formation takes place during days 30-60 and 54-90 of gestation, respectively. Differential expression and expression levels of the genes were studied using microarray technology. Gene activation and repression profiles were studied counting the number of spots with detectable signal. The number of spots for muscle tissue structural protein genes showing upregulated expression increased constantly from day 14 until day 91of gestation indicating continued activation of genes during this period. The mRNA expression level of the genes showed a peak around day 35 of gestation. The expression levels of genes affecting myogenic differentiation (stimulating and inhibiting) showed a peak at day 35 of gestation. The number of spots for differentiation-stimulating genes showing differential expression reaches a first peak around day 35 of gestation and a nadir at day 49 of gestation while the number of spots for differentiation-inhibiting genes reaches a nadir at day 35 of gestation. Myogenic differentiation seems less a matter of the expression level of genes affecting differentiation, but depends on the balance between the number of significantly activated genes for stimulating and inhibiting differentiation. Genes stimulating myoblast proliferation showed a small peak expression prior to day 35 of gestation indicating myoblast proliferation before differentiation. The number of spots and the expression levels of genes for glycolysis and ATP-metabolism are at a nadir around days 35 and 49-63 of gestation suggesting that the energy metabolism is low during fusion of myoblasts into multinucleated muscle fibers.

show abstract

Expression of the insulin-like growth factor II gene in the choroid plexus and the leptomeninges of the adult rat central nervous system.

Cited by 218 publications

References 54 publications

Gestational Choline Deficiency Causes Global and Igf2 Gene DNA Hypermethylation by Up-regulation of Dnmt1 Expression

Gestational Choline Deficiency Causes Global and Igf2 Gene DNA Hypermethylation by Up-regulation of Dnmt1 Expression

Thymic expression of insulin-related genes in an animal model of autoimmune type 1 diabetes

Transcriptome Expression Profiles in Prenatal Pigs in Relation to Myogenesis

Contact Info

Product

Resources

About