Investigation of the functional role of ependymal cilia for congenital hydrocephalus

• Applicant: Dr. Julia Wallmeier
• Subject Area: Pediatric and Adolescent Medicine
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 396725313

Congenital hydrocephalus occurs in about 1:10.000 births, but there is hardly any knowledge about the underlying genetic defects and its pathophysiology.We have shown that genetic defects affecting cilia motility due to ependymal cilia dysfunction cause hydrocephalus in all mutant mice, the prevalence of hydrocephalus in PCD affected individuals harboring orthologous mutations is slightly increased demonstrating that this mechanism also plays a role for human disease. Interestingly, in individuals with MCIDAS mutations, a specific defect affecting ciliogenesis of multiple motile cilia, hydrocephalus is present in nearly all analyzed individuals suggesting that ciliary motility, but also non-motile ciliary functions, are critical to maintain cerebrospinal fluid homeostasis. We therefore plan to examine the clinical phenotype including frequency, clinical picture and disease progression of hydrocephalus in Primary ciliary dyskinesia and Reduced generation of multiple motile cilia affected individuals in detail. We will characterize gene expression profile, protein composition as well as ultrastructure of ependymal cells. Using high-throughput DNA sequencing technologies we will identify hydrocephalus causing genes and characterize their function in regard to ciliogenesis and cilia motility.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Heymut Omran