Abstract
The mammalian central nervous system is a complex neuronal network consisting of a diverse array of cellular subtypes generated in a precise spatial and temporal pattern throughout development. Achieving a greater understanding of the molecular and genetic mechanisms that direct a relatively uniform population of neuroepithelial progenitors into diverse neuronal subtypes remains a significant challenge. The advent of pluripotent stem cell (PSC) technology allows researchers to generate diverse neural populations in vitro. Although the primary focus of PSC-derived neural cells has been their therapeutic potential, utilizing PSCs to study neurodevelopment is another frequently overlooked and equally important application. In this review, we explore the potential for utilizing PSCs to study neural development. We introduce the types of neurodevelopmental questions that PSCs can help to address, and we discuss the different strategies and technologies that researchers use to generate diverse subtypes of PSC-derived neurons. Additionally, we highlight the derivation of several thoroughly characterized neural subtypes; spinal motoneurons, midbrain dopaminergic neurons and cortical neurons. We hope that this review encourages researchers to develop innovative strategies for using PSCs for the study of mammalian, and specifically human, neurodevelopment.
Highlights
How the highly organized human nervous system arises from a relatively uniform population of neural progenitors remains one of the most fascinating and challenging questions in neurobiology
The ability to generate pluripotent stem cell (PSC)-derived neural cells that faithfully recapitulate normal embryonic development enables the study of mammalian neural development, and in particular human, in a more accessible manner has previously been achieved
Rapid progress is being made in manipulating gene expression in PSCs and improving techniques for generating, isolating and studying diverse populations of neural subtypes
Summary
How the highly organized human nervous system arises from a relatively uniform population of neural progenitors remains one of the most fascinating and challenging questions in neurobiology. Another study developed a protocol in which mESCs cultured in the absence of any extrinsic factors produced ∼80% Sox1+ cells, a marker www.frontiersin.org neural induction in vitro without instruction from extrinsic factors, and blocking inhibitors of neural fate can further enhance neurogenesis. When mESCs are cultured in the absence of serum or extrinsic factors (except for a Shh inhibitor), they sequentially generate cortical neurons that grossly recapitulate the temporal pattern of normal development (Eiraku et al, 2008; Gaspard et al, 2008).
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