Abstract
Fate determination in the mammalian telencephalon, with its diversity of neuronal subtypes and relevance to neuropsychiatric disease, remains a critical area of study in neuroscience. Most studies investigating this topic focus on the diversity of neural progenitors within spatial and temporal domains along the lateral ventricles. Often overlooked is whether the location of neurogenesis within a fate-restricted domain is associated with, or instructive for, distinct neuronal fates. Here, we use in vivo fate mapping and the manipulation of neurogenic location to demonstrate that apical versus basal neurogenesis influences the fate determination of major subgroups of cortical interneurons derived from the subcortical telencephalon. Somatostatin-expressing interneurons arise mainly from apical divisions along the ventricular surface, whereas parvalbumin-expressing interneurons originate predominantly from basal divisions in the subventricular zone. As manipulations that shift neurogenic location alter interneuron subclass fate, these results add an additional dimension to the spatial-temporal determinants of neuronal fate determination.
Highlights
One of the most challenging areas in neuroscience is understanding the genetic and extrinsic mechanisms that direct cell fate decisions
Apical progenitors (APs) are biased towards generating SST+ interneurons
To identify medial ganglionic eminence (MGE) progenitors that are biased towards AP divisions, we focused on cells driving reporter expression from the tubulin α-1 promoter. pTα1 is active in neuronal fate-committed progenitors and postmitotic neuronal precursors (Gloster et al, 1999; Mizutani et al, 2007; Sawamoto et al, 2001)
Summary
One of the most challenging areas in neuroscience is understanding the genetic and extrinsic mechanisms that direct cell fate decisions. A higher percentage of all neocortical PV+ interneurons are born later during neurogenesis, inhabit all cortical layers, and display a slight bias for arising from the ventral MGE (vMGE) (Butt et al, 2005; Flames et al, 2007; Inan et al, 2012; Wonders et al, 2008; Xu et al, 2010a) This temporal transition from predominately apical divisions to basal divisions parallels the shift in generation of SST+ to PV+ interneurons, raising the question as to whether apical or basal neurogenic divisions preferentially give rise to SST+ and PV+ interneurons, respectively
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