How to make striatal projection neurons

Abstract

Medium spiny neurons (MSNs) are the main projection neurons of the striatum and are preferentially lost in Huntington’s disease (HD). With no current cure for this neurodegenerative disorder, the specificity of neuronal loss in the striatum makes cell transplantation therapy an attractive avenue for its treatment. Also, given that MSNs are particularly vulnerable in HD, it is necessary to understand why these neurons degenerate in order to develop new therapeutic options. Both approaches require access to human MSN progenitors and their mature neuronal derivatives. Human embryonic stem cells and HD patient induced pluripotent stem cells (together referred to as hPSCs) may serve as an unlimited source of such tissue if they can be directed toward authentic striatal neuronal lineage. Understanding the MSN differentiation pathway in the brain is therefore of paramount importance for the generation of accurate protocols to obtain striatal cells in vitro. The focus of this mini review will be on striatal development and current methods to generate MSNs from hPSCs.