Identifying the steps involved in striatal development is important both for understanding the striatum in health and disease, and for generating protocols to differentiate striatal neurons for regenerative medicine. The most prominent neuronal subtype in the adult striatum is the medium spiny projection neuron (MSN), which constitutes more than 85% of all striatal neurons and classically expresses DARPP-32. Through a microarray study of genes expressed in the whole ganglionic eminence (WGE: the developing striatum) in the mouse, we identified the gene encoding the transcription factor Forkhead box protein P1 (FoxP1) as the most highly up-regulated gene, thus providing unbiased evidence for the association of FoxP1 with MSN development. We also describe the expression of FoxP1 in the human fetal brain over equivalent gestational stages. FoxP1 expression persisted through into adulthood in the mouse brain, where it co-localised with all striatal DARPP-32 positive projection neurons and a small population of DARPP-32 negative cells. There was no co-localisation of FoxP1 with any interneuron markers. FoxP1 was detectable in primary fetal striatal cells following dissection, culture, and transplantation into the adult lesioned striatum, demonstrating its utility as an MSN marker for transplantation studies. Furthermore, DARPP-32 expression was absent from FoxP1 knock-out mouse WGE differentiated in vitro, suggesting that FoxP1 is important for the development of DARPP-32-positive MSNs. In summary, we show that FoxP1 labels MSN precursors prior to the expression of DARPP-32 during normal development, and in addition suggest that FoxP1 labels a sub-population of MSNs that are not co-labelled by DARPP-32. We demonstrate the utility of FoxP1 to label MSNs in vitro and following neural transplantation, and show that FoxP1 is required for DARPP-32 positive MSN differentiation in vitro.
- Klíčová slova
- DARPP-32, FoxP1, Huntington's disease, Medium spiny neurons, Neural transplantation,
- MeSH
- buněčná diferenciace fyziologie MeSH
- corpus striatum * cytologie embryologie růst a vývoj MeSH
- dopaminem a cAMP regulovaný fosfoprotein 32 metabolismus MeSH
- embryo savčí MeSH
- endodeoxyribonukleasy MeSH
- forkhead transkripční faktory genetika metabolismus MeSH
- jaderné proteiny metabolismus MeSH
- kultivované buňky MeSH
- myši knockoutované MeSH
- myši MeSH
- neparametrická statistika MeSH
- nervové kmenové buňky fyziologie transplantace MeSH
- neurony cytologie metabolismus MeSH
- novorozená zvířata MeSH
- plod cytologie MeSH
- proteiny nervové tkáně metabolismus MeSH
- represorové proteiny genetika metabolismus MeSH
- techniky in vitro MeSH
- transportní proteiny metabolismus MeSH
- vývojová regulace genové exprese fyziologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- dopaminem a cAMP regulovaný fosfoprotein 32 MeSH
- endodeoxyribonukleasy MeSH
- forkhead transkripční faktory MeSH
- FOXP1 protein, human MeSH Prohlížeč
- jaderné proteiny MeSH
- proteiny nervové tkáně MeSH
- RBBP8 protein, human MeSH Prohlížeč
- represorové proteiny MeSH
- transportní proteiny MeSH
MicroRNAs (miRNAs) translationally repressing their target messenger RNAs due to their gene-regulatory functions play an important but not unexpected role in a tumour development. More surprising are the findings that levels of various miRNAs are well correlated with presence of specific tumours and formation of metastases. Moreover, these small regulatory molecules play a role in the resistance of cancer cells to commonly used anti-cancer drugs, such as cisplatin, anthracyclines, and taxanes. In that respect, miRNAs become very attractive target for potential therapeutic interventions. Improvements in the sensitivity of miRNAs detection techniques led to discovery of circulating miRNAs which became very attractive non-invasive biomarker of cancer with a substantial predictive value. In this review, the authors focus on i) oncogenic and anti-tumour acting miRNAs, ii) function of miRNAs in tumour progression, iii) possible role of miRNAs in resistance to anticancer drugs, and iv) diagnostic potential of miRNAs for identification of cancer from circulating miRNAs with special emphasis on prostate cancer. Moreover, relationship between miRNAs and expression of metallothionein is discussed as a possible explanation of resistance against platinum based drugs.
- MeSH
- chemorezistence MeSH
- cytostatické látky farmakologie MeSH
- lidé MeSH
- metalothionein genetika metabolismus MeSH
- mikro RNA genetika metabolismus MeSH
- nádory prostaty diagnóza farmakoterapie genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- cytostatické látky MeSH
- metalothionein MeSH
- mikro RNA MeSH
BACKGROUND: Friedreich's ataxia is an autosomal recessive, neurodegenerative disease with a prevalence of 1-2: 100,000. Ninety five % of cases are caused by Friedreich's ataxia expansion of GAA triplet repeat in the first intron of the X25 gene. The gene is mapped on chromosome 9q. The objective of the investigation was to introduce simple and reliable DNA diagnosis helping to specify of spinocerebellare ataxias. METHODS AND RESULTS: Our diagnosis is based on the differentiation of normal and mutant alleles of gene X25 with PCR and electrophoresis on agarose gel. Size of PCR product of normal allele is in our case 521-614 bp. It is responding to 7-38 GAA triplets. Size of mutant alleles with 200-1200 GAA triplets is as 4100 bp. After the method was introduced, we analysed 12 probands. Four of them suffered from Friedreich's ataxia. CONCLUSIONS: We introduced a fast, non-radioactive, reliable DNA diagnostic method. The contribution of this method is defection of carriers and we can screen of families with the risk of Friedreich's ataxia.
We report on the haplotype analysis with polymorphic repeat markers DXS548 and FRAXAC1 next to the FMR1 gene in 37 unrelated fragile X and 36 control chromosomes from Bohemia and Moravia. Our results suggest a significant linkage disequilibrium between fragile X mutations and certain DXS548-FRAXAC1 haplotypes. Allele frequencies obtained differ slightly from those of other European populations with allele 194 being less frequent in our control sample. Rare DXS548 alleles 6.5 (195) and 0 (208) were also present.
- MeSH
- alely MeSH
- haplotypy MeSH
- lidé MeSH
- populační genetika MeSH
- protein FMRP MeSH
- proteiny nervové tkáně genetika MeSH
- proteiny vázající RNA * MeSH
- syndrom fragilního X genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- FMR1 protein, human MeSH Prohlížeč
- protein FMRP MeSH
- proteiny nervové tkáně MeSH
- proteiny vázající RNA * MeSH
BACKGROUND: Familial hypercholesterolemia is one of the most frequent hereditary metabolic diseases. As a result of the functional disorder of the molecule of the LDL receptor LDL cholesterol is not sufficiently eliminated from the blood stream and exerts an atherogenic effect. The objective of the study was to introduce direct detection of mutations in the gene for the LDL receptor and characterize the spectrum of mutations in the Czech population. METHODS AND RESULTS: The authors analyzed a group of 84 unrelated patients where on the basis of clinical and biochemical criteria the diagnosis of FH was established. From the group 12 patients were eliminated (14.3%) where a mutation 3500 in the gene for apolipoprotein (apo) B-100 was detected. This mutation is most frequently the cause of a familial defect of apo B-100 (FDB), which cannot be differentiated clinically or biochemically from FH. In the LDL receptor gene a total of 11 mutations were found in 14 unrelated patients (16.7%), incl. 7 mutations not described hitherto. CONCLUSIONS: This is the first systematic characteristic of the spectrum of mutations in the LDL receptor gene in the Czech population. Molecular genetic analysis of the gene for the LDL receptor in affected families can contribute towards early assessment of the diagnosis of FH and thus to prevention of life threatening cardiovascular episodes in asymptomatic subjects.
- MeSH
- apolipoprotein B-100 MeSH
- apolipoproteiny B genetika MeSH
- hyperlipoproteinemie typ II genetika MeSH
- LDL-receptory genetika MeSH
- lidé MeSH
- mutace * MeSH
- polymerázová řetězová reakce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- apolipoprotein B-100 MeSH
- apolipoproteiny B MeSH
- LDL-receptory MeSH
Forty Duchenne muscular dystrophy patients from the province of Moravia in the Czech Republic, who were previously found negative for large deletions in the dystrophin gene, were tested for the presence of point mutations in selected exons. Besides several intron and exon polymorphisms, two cases of nonsense mutations were detected in exon 70, thus causing the loss of the C-terminal domain of dystrophin. One of these, the mutation, S3365X, is newly reported here while the other, R3381X, has been described previously. These mutations, only 16 bp distant from each other, have a very different impact on the mental abilities of the corresponding patients.
- MeSH
- bodová mutace * MeSH
- dítě MeSH
- dystrofin genetika MeSH
- elektroforéza v polyakrylamidovém gelu MeSH
- lidé MeSH
- mentální retardace komplikace genetika MeSH
- polymerázová řetězová reakce MeSH
- polymorfismus konformace jednovláknové DNA MeSH
- svalové dystrofie komplikace genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dystrofin MeSH
