[S7.1]: Control of cortical development by the meninges

The mesenchymal covering of the brain – the meninges – has long been considered primarily a protective structure with prominent functions related to CSF circulation and formation of the blood brain barrier. However, studies from my laboratory and others now support several critical functions for meningeal cortical interactions during development. One long recognized such role involves the role of the meninges in forming the cortical basement membrane. When the basement membrane breaks down or is misformed due to mutations in structural extracellular matrix proteins prominent cortical malformations due to disordered radial migration form. In my laboratory we have been particularly interested in instructive roles that secreted cues produced by the meninges might control during development. Some years ago we showed that Cxcl12 secreted by the meninges is a potent regulator of laminar position of cortical interneurons, Cajal-Retzius cells and dentate progenitors during their migratory routes. More recently, we have shown that retinoic acid produced and secreted by the meninges regulate embryonic cortical neurogenesis. We have now obtained evidence that morphogenic signals produced by the meninges control the formation of midline structures critical for corpus callosum formation and that meningeal cues also regulate the production of axon guidance cues within the brain. In this lecture I will discuss the multiple roles of the meninges in regulating cortical development and how breakdown in these functions can lead to prominent cortical malformations.