Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Hum Genet
2014 Aug 01;1338:997-1009. doi: 10.1007/s00439-014-1444-2.
Show Gene links
Show Anatomy links
CHD7, the gene mutated in CHARGE syndrome, regulates genes involved in neural crest cell guidance.
Schulz Y, Wehner P, Opitz L, Salinas-Riester G, Bongers EM, van Ravenswaaij-Arts CM, Wincent J, Schoumans J, Kohlhase J, Borchers A, Pauli S.
???displayArticle.abstract???
Heterozygous loss of function mutations in CHD7 (chromodomain helicase DNA-binding protein 7) lead to CHARGE syndrome, a complex developmental disorder affecting craniofacial structures, cranial nerves and several organ systems. 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 are unknown. Therefore, we undertook a genome-wide microarray expression analysis on wild-type and CHD7 deficient (Chd7 (Whi/+) and Chd7 (Whi/Whi)) mouse embryos at day 9.5, a time point of neural crest cell migration. We identified 98 differentially expressed genes between wild-type and Chd7 (Whi/Whi) embryos. Interestingly, many misregulated genes are involved in neural crest cell and axon guidance such as semaphorins and ephrin receptors. By performing knockdown experiments for Chd7 in Xenopus laevis embryos, we found abnormalities in the expression pattern of Sema3a, a protein involved in the pathogenesis of Kallmann syndrome, in vivo. In addition, we detected non-synonymous SEMA3A variations in 3 out of 45 CHD7-negative CHARGE patients. In summary, we discovered for the first time that Chd7 regulates genes involved in neural crest cell guidance, demonstrating a new aspect in the pathogenesis of CHARGE syndrome. Furthermore, we showed for Sema3a a conserved regulatory mechanism across different species, highlighting its significance during development. Although we postulated that the non-synonymous SEMA3A variants which we found in CHD7-negative CHARGE patients alone are not sufficient to produce the phenotype, we suggest an important modifier role for SEMA3A in the pathogenesis of this multiple malformation syndrome.
Aramaki,
Phenotypic spectrum of CHARGE syndrome with CHD7 mutations.
2006, Pubmed
Aramaki,
Phenotypic spectrum of CHARGE syndrome with CHD7 mutations.
2006,
Pubmed Bajpai,
CHD7 cooperates with PBAF to control multipotent neural crest formation.
2010,
Pubmed
,
Xenbase Bergman,
CHD7 mutations and CHARGE syndrome: the clinical implications of an expanding phenotype.
2011,
Pubmed Borchers,
Xenopus cadherin-11 restrains cranial neural crest migration and influences neural crest specification.
2001,
Pubmed
,
Xenbase Bosman,
Multiple mutations in mouse Chd7 provide models for CHARGE syndrome.
2005,
Pubmed Chalouhi,
Olfactory evaluation in children: application to the CHARGE syndrome.
2005,
Pubmed Dodé,
Kallmann syndrome.
2009,
Pubmed Gammill,
Neural crest specification: migrating into genomics.
2003,
Pubmed Hall,
The neural crest as a fourth germ layer and vertebrates as quadroblastic not triploblastic.
2000,
Pubmed Hanchate,
SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome.
2012,
Pubmed Harland,
In situ hybridization: an improved whole-mount method for Xenopus embryos.
1991,
Pubmed
,
Xenbase Hawker,
Two new mouse mutants with vestibular defects that map to the highly mutable locus on chromosome 4.
2005,
Pubmed Hrabé de Angelis,
Genome-wide, large-scale production of mutant mice by ENU mutagenesis.
2000,
Pubmed Huang,
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.
2009,
Pubmed Huang,
Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists.
2009,
Pubmed Janssen,
Mutation update on the CHD7 gene involved in CHARGE syndrome.
2012,
Pubmed Jongmans,
CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene.
2006,
Pubmed Jongmans,
CHD7 mutations in patients initially diagnosed with Kallmann syndrome--the clinical overlap with CHARGE syndrome.
2009,
Pubmed Kim,
Mutations in CHD7, encoding a chromatin-remodeling protein, cause idiopathic hypogonadotropic hypogonadism and Kallmann syndrome.
2008,
Pubmed Kirby,
Factors controlling cardiac neural crest cell migration.
2010,
Pubmed Koestner,
Semaphorin and neuropilin expression during early morphogenesis of Xenopus laevis.
2008,
Pubmed
,
Xenbase Lalani,
Spectrum of CHD7 mutations in 110 individuals with CHARGE syndrome and genotype-phenotype correlation.
2006,
Pubmed Morgan,
Ear-nose-throat abnormalities in the CHARGE association.
1993,
Pubmed Ogata,
Kallmann syndrome phenotype in a female patient with CHARGE syndrome and CHD7 mutation.
2006,
Pubmed Opitz,
Impact of RNA degradation on gene expression profiling.
2010,
Pubmed Pinto,
CHARGE syndrome includes hypogonadotropic hypogonadism and abnormal olfactory bulb development.
2005,
Pubmed Randall,
Great vessel development requires biallelic expression of Chd7 and Tbx1 in pharyngeal ectoderm in mice.
2009,
Pubmed Sanlaville,
CHARGE syndrome: an update.
2007,
Pubmed Sanlaville,
Phenotypic spectrum of CHARGE syndrome in fetuses with CHD7 truncating mutations correlates with expression during human development.
2006,
Pubmed Schwanzel-Fukuda,
Origin of luteinizing hormone-releasing hormone neurons.
1989,
Pubmed Siebert,
Pathologic features of the CHARGE association: support for involvement of the neural crest.
1985,
Pubmed Smith,
Injected Xwnt-8 RNA acts early in Xenopus embryos to promote formation of a vegetal dorsalizing center.
1991,
Pubmed
,
Xenbase Teixeira,
Defective migration of neuroendocrine GnRH cells in human arrhinencephalic conditions.
2010,
Pubmed Van Meter,
Oculo-auriculo-vertebral spectrum and the CHARGE association: clinical evidence for a common pathogenetic mechanism.
1996,
Pubmed Vissers,
Mutations in a new member of the chromodomain gene family cause CHARGE syndrome.
2004,
Pubmed Williams,
Speculations on the pathogenesis of CHARGE syndrome.
2005,
Pubmed Wincent,
CHD7 mutation spectrum in 28 Swedish patients diagnosed with CHARGE syndrome.
2008,
Pubmed Yazdani,
The semaphorins.
2006,
Pubmed Young,
SEMA3A deletion in a family with Kallmann syndrome validates the role of semaphorin 3A in human puberty and olfactory system development.
2012,
Pubmed
