QBI Neuroscience Seminar: 'WNT signalling in choroid plexus development'
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- Dr Michael Hodges-Langford, Queensland Brain Institute, University of Queensland
Title: “WNT signalling in choroid plexus development”
Abstract: The choroid plexuses are highly vascularized epithelial tissues responsible for producing the majority of the cerebrospinal fluid that circulates throughout the ventricular system of the brain. From foetal life to advanced aging, the choroid plexuses perform a multitude of functions essential for brain development, homeostasis and health, ranging from supplying the brain with micronutrients and neurotrophic factors, to protecting the brain against neurotoxic biochemical and pathogenic insults. However, despite the diverse and vital roles performed by the choroid plexuses, surprisingly little is known about the cellular and molecular mechanisms that govern their development.
In this talk, I will present our recent work examining the role of WNT signalling in choroid plexus development. Using knockout mice, we have found that the secreted WNT protein, WNT5a, controls the morphological transformation of primitive pseudostratified neuroepithelia into the highly specialised transport epithelia of the choroid plexuses. Furthermore, we have also identified a role for WNT5a in coordinating the migration of mesenchymal cells into the developing choroid plexuses. Mechanistically, we find that the choroid plexus phenotype observed in Wnt5a knockout mice is recapitulated in mice deficient for the WNT5a receptor, RYK, as well as by the in vivo pharmacological inhibition of Rho-associated kinase (ROCK), a downstream component of the planar cell polarity pathway. We propose that WNT5a/RYK signalling via the planar cell polarity pathway is essential for orchestrating the complex morphogenetic events underpinning the development of the choroid plexuses.
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