The brain ventricles are a highly conserved system of cavities containing cerebrospinal fluid that are required for normal brain function. Abnormalities in brain ventricle structure can lead to hydrocephaly and have been correlated with many mental health disorders including autism and schizophrenia. My research investigates the genetic and molecular mechanisms underlying brain ventricle development, using a forward genetic approach in the zebrafish system. The zebrafish is an excellent model for this study, as the brain ventricles are visible throughout development, and many genetic, molecular, and embryological tools are available. A major part of my work consists of identifying and characterizing brain ventricle mutants, by analyzing in detail a set of previously identified but poorly studied ventricle mutants. Following initial characterization, the genetic pathways necessary for ventricle opening will be constructed, and one or more genes will be selected for further molecular analysis. This analysis will exploit the zebrafish to identify genes that are required to build normal brain structure and which may be perturbed in mental health disorders.


Figure: Timecourse of zebrafish brain ventricle formation. Ventricles were visualized by microinjecting a fluorescent dye-Texas Red-dextran into the hindbrain ventricle of anesthetized embryos. (a) Ventricle injection schematic: lateral view of 24 hpf embryo with microinjection needle entering hindbrain ventricle. (b-g) Developmental profile of brain ventricle morphology (dorsal views, anterior to left). Heart beat onset at 24 hpf, after brain ventricles have formed. Inset: lateral view of embryo.