Dynamics of RNA transport and local translation in radial glia
Radial glia progenitors are polarized, with a cell body near the ventricle and extending from this a long basal process which forms endfeet at the top of the brain. Signals nearby the endfeet, within a local niche, can influence progenitors through poorly understood mechanisms. The morphology of radial glia inspired us to investigate roles for mRNA localization in these cells. We used live imaging to discover that mRNAs are actively transported within radial glia, to the top of the brain, where they can be locally translated into protein! RNA transport is dependent upon FMRP, an RNA binding protein that is responsible for Fragile X syndrome. Learn more about this first study in Current Biology, and in an accompanying preview, on the Node, by Autism focused Simons Foundation, and in a review we wrote for FEBs Letters.We also recently wrote a review for Traffic in which we discuss parallels between RNA localization in radial glia and throughout the nervous system.
What is the function of RNA localization and local translation?
We are actively working to understand the function of localized mRNAs in the developing brain. We recently discovered new roles for Arhgap11a localization in radial glial morphology and cortical interneuron positioning. For this we employed knockdown approaches, rescue experiments, and extensive imaging (confocal, live brain slices, EM). This was published in a recent study in Neuron and also featured on the cover.
We have used in vivo proximity ligation to discover for the first time subcellular proteomes of radial glia. This highlights outstanding candidates for functional manipulation. We used mouse genetics to deplete myosins enriched in endfeet-from this we showed that endfeet are essential for organizing interneurons in the marginal zone. This is published in PLOS Biology and featured in a preview.
We continue to investigate this fascinating new world of gene regulation in radial glia. For example, we are studying what mRNAs are localized to these distal structures and translated, how these processes are regulated intrinsically and extrinsically, and how this impacts neurogenesis!
