Elucidation of the pathogenesis of Dandy-Walker malformation

• Applicant: Dr. Anne Gregor
• Subject Area: Human Genetics
• Term: from 2015 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 273224692

Dandy-Walker malformation (DWM) is one of the most common cerebellar malformations and is characterized by hypoplasia and upward rotation of the cerebellar vermis and a cystic dilatation of the fourth ventricle with an enlarged posterior fossa. The pathomechanisms involved in DWM and in hindbrain malformations in general are still largely unknown. Recently, the Gleeson laboratory has identified homozygous truncating mutations affecting a novel, previously not disease-associated gene in two unrelated families with DWM and cloaca. In this research project I will study the function of this protein using expression and localization studies in patient-derived induced pluripotent stem cells or induced neurons, chromatin- and co-immunoprecipitation and possibly mass-spectrometry. Additionally, zebrafish and CRISPR/Cas9-generated knockout mice will be used as model organisms toelucidate the role of the identified protein in the pathogenesis of DWM. Insights into the function of this protein and the role of its loss-of-function in DWM may lead to a better understanding of pathways involved in hindbrain malformations.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Joseph Gleeson