Proceedings of The Physiological Society

King's College London (2011) Proc Physiol Soc 22, C01

Oral Communications

The role of fascin and drebrin in neuroblast migration

M. Sonego1, S. Gajendra1, R. Hendricusdottir3, B. Eickholt3, M. Parsons2, P. Doherty1, G. Lalli1

1. Wolfson CARD, King's College London, London, london, United Kingdom. 2. MRC Centre for Developmental Neurobiology, King's College London, London, London, United Kingdom. 3. Randall Division of Cell and Molecular Biology, King's College London, London, London, United Kingdom.


Adult neurogenesis persists in the subventricular zone (SVZ), a crucial brain area that can respond to insults by producing neuronal progenitor cells able to migrate to sites affected by injury and neurodegeneration. Understanding the property of these cells is essential to fully elucidate their potential in neuroregenerative strategies. In the past few years several factors regulating neuronal migration have been identified, however still very little is known about the exact molecular mechanisms controlling neural progenitor motility. In this study we investigate the function of two proteins, fascin and drebrin, which are highly expressed in the postnatal brain by SVZ-derived migrating neuroblasts. Fascin is an actin-bundling protein that contributes to the architecture and function of cell protrusions in cell adhesion, interaction and motility. Drebrin is expressed by migrating neuroblasts; interestingly, cessation of migration in these cells coincides with the disappearance of the protein. We show here that RNAi-mediated depletion of fascin significantly impairs neuroblast migration in vitro. Phosphorylation of fascin on Ser39 is important for its actin-bundling activity and is regulated by protein kinase C (PKC). We demonstrate that Ser39 phosphorylation plays a fundamental role in neuroblast migration. Indeed, the migration of neuroblasts is strongly impaired when these cells are nucleofected either with a phosphomimetic (S39D) or a non-phosphorylatable (S39A) fascin variant, pointing to a crucial role for PKC in the regulation of neuroblast motility. Importantly, these cells still retain the ability to extend a protrusion in the direction of migration. Similarly, drebrin knockdown also substantially impairs neural progenitor migration in vitro and leads to a highly branched, unpolarised neuroblast morphology. We are currently validating our findings in vivo by performing postnatal electroporation of shRNA-expressing plasmids and time-lapse imaging of cultured brain slices from CD1 lactating P3 mouse pups. Our preliminary observations strongly suggest that drebrin depletion may severely affect neuroblast morphology also in vivo. In summary, both fascin and drebrin appear to play a fundamental function by controlling neural progenitor motility and morphology. Our future studies will aim at elucidating the signalling pathways involving both proteins during neural progenitor migration.

Where applicable, experiments conform with Society ethical requirements