From Progenitors to Progeny: Shaping Striatal Circuit Development and Function

Abstract

Understanding how neurons of the striatum are formed and integrate into complex synaptic circuits is essential to provide insight into striatal function in health and disease. In this review, we summarize our current understanding of the development of striatal neurons and associated circuits with a focus on their embryonic origin. Specifically, we address the role of distinct types of embryonic progenitors, found in the proliferative zones of the ganglionic eminences in the ventral telencephalon, in the generation of diverse striatal interneurons and projection neurons. Indeed, recent evidence would suggest that embryonic progenitor origin dictates key characteristics of postnatal cells, including their neurochemical content, their location within striatum, and their long-range synaptic inputs. We also integrate recent observations regarding embryonic progenitors in cortical and other regions and discuss how this might inform future research on the ganglionic eminences. Last, we examine how embryonic progenitor dysfunction can alter striatal formation, as exemplified in Huntington's disease and autism spectrum disorder, and how increased understanding of embryonic progenitors can have significant implications for future research directions and the development of improved therapeutic options.SIGNIFICANCE STATEMENT This review highlights recently defined novel roles for embryonic progenitor cells in shaping the functional properties of both projection neurons and interneurons of the striatum. It outlines the developmental mechanisms that guide neuronal development from progenitors in the embryonic ganglionic eminences to progeny in the striatum. Where questions remain open, we integrate observations from cortex and other regions to present possible avenues for future research. Last, we provide a progenitor-centric perspective onto both Huntington's disease and autism spectrum disorder. We suggest that future investigations and manipulations of embryonic progenitor cells in both research and clinical settings will likely require careful consideration of their great intrinsic diversity and neurogenic potential.

Keywords: basal ganglia; embryonic progenitors; interneurons; lateral ganglionic eminence; medial ganglionic eminence; neuronal diversity; spiny projection neurons; striatum.