title: Deterioration of the transcriptional, splicing and elongation machinery in brain of fetal Down syndrome.
abstract: Perturbation of brain development i.e. regulation of gene expression, differentiation, growth and migration in Down Syndrome (DS) has been reported to occur early in life pointing to impairment of the complex system of transcription and or translation and indeed, altered expression of transcription factors has been reported in adult DS brain. We therefore decided to compare the transcriptional and translational machinery in cortex of brains of controls and fetuses with Down syndrome in the second trimenon of gestation. We determined a series of transcription/translation factors by 2 D-electrophoresis followed by MALDI--identification and quantification with specific software. The protooncogene C-CRK, CRK-like protein, elongation factor 1-alpha 1, elongation factor 2, elongation factor tu and two out of four spots representing PTB-associated splicing factor PSF were significantly downregulated in brain of fetal DS fetuses as compared to controls. The finding of reduced transcription and translation factors may indicate deranged protein synthesis. The underlying cause for individual reduced transcription, splicing and translation factors may be explained by chromosomal imbalance or by posttranslational modifications as e.g. phosphorylation, known to be aberrant in DS. Reduced expression of transcription factors in fetal DS during early life may be responsible or reflecting impaired brain development and deficient wiring of the brain in DS.
authors.affiliation: Department of Pediatrics, University of Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Freidl
authors.forename: T
authors.initials: T
authors.lastname: Gulesserian
authors.forename: G
authors.initials: G
authors.lastname: Lubec
authors.forename: M
authors.initials: M
authors.lastname: Fountoulakis
authors.forename: B
authors.initials: B
authors.lastname: Lubec
mesh_terms: D001921:Brain / Q000002:abnormalities* / Q000502:physiology*; D004314:Down Syndrome / Q000235:genetics* / Q000503:physiopathology*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005333:Fetus / Q000002:abnormalities / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D020648:Peptide Elongation Factor 1 / Q000235:genetics; D020652:Peptide Elongation Factor 2 / Q000235:genetics; D010444:Peptide Elongation Factor Tu / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D020543:Proteome / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D050737:Proto-Oncogene Proteins c-crk; D012326:RNA Splicing / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D020648:Peptide Elongation Factor 1; D020652:Peptide Elongation Factor 2; D020543:Proteome; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D010444:Peptide Elongation Factor Tu