1. Yale University Receives a NIH Grant for Xenopus As A Model System for Hydrocephaly and Ependymal Ciliogenesis

    Yale University Receives a NIH Grant for Xenopus As A Model System for Hydrocephaly and Ependymal Ciliogenesis

    Yale University Receives a 2020 NIH Grant for $236,175 for Xenopus As A Model System for Hydrocephaly and Ependymal Ciliogenesis. The principal investigator is Engin Deniz. Below is a summary of the proposed work.

    Congenital Hydrocephalus (CH), the pathological expansion of the cerebral ventricles due to cerebrospinal fluid (CSF) accumulation, is a common birth defect (1 in every 1000 births) with high mortality and morbidity. In fact, CH is the most common disease treated by pediatric neurosurgeons and despite advances in surgical technique, palliation in many patients remains inadequate. In part, these challenging cases may be due to our incomplete understanding of hydrocephalus pathogenesis. While advances in genomics are beginning to identify candidate genes that may cause CH, we lack genetically tractable animal models where pathogenesis can be analyzed. In our recent work, we paired optical coherence tomography imaging (OCT) with the frog Xenopus tropicalis to model human congenital hydrocephalus. We demonstrated that OCT imaging of mutant tadpoles can readily detect hallmarks of human hydrocephalus including aquaductal stenosis and/or ventriculomegaly. In this proposal, we seek to further advance this model and develop Xenopus as a model system that can evaluate CH candidate genes and distinguish ciliary vs. non-ciliary pathogenesis mechanisms. Our central hypothesis is that the pathogenesis of CH due to ciliary vs. non-ciliary mechanisms will be discretely different with respect to ventricular morphology, CSF flow network, and neural progenitor cell fate, which can have important implications for treatment.

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