STEMCELLSTONEURONS · Dissecting the role of Activin signalling in the acquisition of neuronal subtype identity in the telencephalon of the mammalian embryo

Understanding the molecular control of neuronal differentiation is critical for the safe and effective use of embryonic stem cells (ESCs) for regenerative medicine and for generating the correct cell types for disease modelling. A central step in the neural differentiation process is the generation of neurons with different subtype identity. In this project we will address how telencephalic neural progenitors acquire specific neuronal fates using the mouse embryo and mouse ESCs. To achieve this we will dissect the pathways that regulate neural differentiation and in particular, those involved in the acquisition of neuronal identity within the telencephalon. We will focus on Activin signalling, that we have previously shown to control interneuron specification. We will (i) study how Activin signalling controls neuronal fate and differentiation in vivo, (ii) identify the targets of Activin signalling within the developing telencephalon, (iii) develop novel protocols for the differentiation of ESCs into neuronal subtypes that are of interest to regenerative medicine, and (iv) examine how Activin cross-talks with the other main signalling pathways that control neuronal identity in the telencephalon, the Shh and Fgf pathways. Our results will not only shed important light on the molecular mechanisms regulating the acquisition of identity of neuronal subtypes that are affected in a wide variety of neurodegenerative diseases, but will also establish novel protocols for the differentiation of ESCs into these neuronal subtypes, having in this way a direct impact in regenerative medicine.