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| Status |
Public on Jul 01, 2014 |
| Title |
CHD7 regulates gene networks involved in neural crest cell migration and axon guidance |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Heterozygous loss-of function mutations in CHD7 (chromodomain helicase DNA-binding protein 7) lead to CHARGE syndrome, a complex developmental disorder affecting craniofacial structures, peripheral nerves and several organ systems like eyes, ears, nose and heart. Recently, it was demonstrated that CHD7 is essential for the formation of multipotent migratory neural crest cells, which migrate from the neural tube to many regions of the embryo, where they differentiate into various tissues including craniofacial and heart structures. So far only few CHD7 target genes involved in neural crest cell development have been identified and the role of CHD7 in neural crest cell guidance and the regulation of mesenchymal-epithelial transition is unknown. Therefore, we undertook a genome-wide microarray expression analysis on wild-type and CHD7 deficient (Chd7Whi/+ and Chd7Whi/Whi) mouse embryos at day 9.5, the time point of neural crest cell migration. We identified 98 genes showing greater than two fold differences in expression (log2 fold-change) and a P-value to false discovery rate (FDR) < 0.05 between wild-type and Chd7Whi/Whi embryos. Interestingly, many misregulated genes are involved in neural crest cell and axon guidance like semaphorins and ephrin receptors. By performing knockdown experiments for Chd7 and one of its target genes, namely semaphorin3a in Xenopus laevis embryos, we could show abnormalities in the migration of neural crest cells in vivo. Additionally, we detected non-synonymous SEMA3A variations in 3 out of 45 CHD7 negative CHARGE patients suggesting a role for SEMA3A in the pathogenesis of CHARGE syndrome.
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| Overall design |
To identify genes that are affected by the absence of functional Chd7 at the time point of neural crest cell migration, the expression profiles of E9.5 wild-type, Chd7Whi/+ and Chd7Whi/Whi female mouse embryos were compared by whole-genome microarray analysis. Mouse embryos of the same sex were used to avoid sex-dependent gene expression effects. We performed microarray analysis by using the Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Agilent) on four biological replicates from each group.
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| Contributor(s) |
Schulz Y, Wehner P, Opitz L, Salinas-Riester G, Bongers E, Ravenswaaij-Arts C, Wincent J, Schoumans J, Kohlhase J, Borchers A, Pauli S |
| Citation missing |
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| Submission date |
May 02, 2013 |
| Last update date |
Jan 19, 2018 |
| Contact name |
Gabriela Salinas |
| E-mail(s) |
Gabriela.Salinas-Riester@medizin.uni-goettingen.de
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| Organization name |
Universitaetsmedizin Goettingen
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| Department |
Department of Pathology
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| Lab |
NGS Integrative Genomics
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| Street address |
Kreuzbergring 57
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| City |
Goettingen |
| State/province |
Lower-Saxony |
| ZIP/Postal code |
37075 |
| Country |
Germany |
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| Platforms (1) |
| GPL10333 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Feature Number version) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA201065 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE46591_RAW.tar |
32.5 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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