Delineation of Multiple Subpallial Progenitor Domains by the Combinatorial Expression of Transcriptional Codes

Abstract

The mammalian telencephalon is considered the most complex of all biological structures. It comprises a large number of functionally and morphologically distinct types of neurons that coordinately control most aspects of cognition and behavior. The subpallium, for example, not only gives rise to multiple neuronal types that form the basal ganglia and parts of the amygdala and septum but also is the origin of an astonishing diversity of cortical interneurons. Despite our detailed knowledge on the molecular, morphological, and physiological properties of most of these neuronal populations, the mechanisms underlying their generation are still poorly understood. Here, we comprehensively analyzed the expression patterns of several transcription factors in the ventricular zone of the developing subpallium in the mouse to generate a detailed molecular map of the different progenitor domains present in this region. Our study demonstrates that the ventricular zone of the mouse subpallium contains at least 18 domains that are uniquely defined by the combinatorial expression of several transcription factors. Furthermore, the results of microtransplantation experiments in vivo corroborate that anatomically defined regions of the mouse subpallium, such as the medial ganglionic eminence, can be subdivided into functionally distinct domains.

Interneuron Progenitors Attenuate the Power of Acute Focal Ictal Discharges

“…Previous studies have shown that transplants of dorsal or ventral regions of E13.5 MGE, placed into the isochronic MGE in utero [16], or into the neonatal neocortex [15], result in a bias in favor of SST+interneurons in the dMGE transplants, and PV+interneurons in the vMGE transplants. In this study, however, we did not see evidence for this bias (Fig.…”

“…Although species differences with primates appear to exist, in rodents and ferrets most cortical interneurons, including the PV and the SST expressing subgroups, originate in the medial ganglionic eminence (MGE) of the subcortical telencephalon [14]. Genetic fatemapping and transplantation studies indicate that within the MGE there is a bias for PV or SST expressing interneurons to originate from ventral or dorsal MGE regions, respectively [15][16][17]. Transplanted MGE cells not only differentiate into mature GABAergic (gamma-aminobutyric-acid-releasing) interneurons, but also form inhibitory synapses that increase GABAergic synaptic transmission onto adjacent pyramidal cells [18] and alter cortical pyramidal neuron plasticity [19].…”

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

“…Progenitors in the subventricular zone that produce projection neurons express diverse combinations of transcription factors that guide them from proliferation through differentiation into unique types of cells (Greig et al, 2013;Molyneaux et al, 2007). Similarly, GABAergic interneuron types are predetermined based on unique transcription factor combinations in different progenitor types in the subpallial ganglionic eminences (Flames et al, 2007;Wonders and Anderson, 2006). However, migration patterns of glutamatergic projection neurons and GABAergic interneurons are quite different: while projection neurons migrate radially and remain in the general area where they were born, interneurons have a predominantly tangential migration, and integrate into regions far away from their origins (Bystron et al, 2008;Guo and Anton, 2014;Marin and Rubenstein, 2003;Nadarajah and Parnavelas, 2002).…”

From sauropsids to mammals and back: New approaches to comparative cortical development

“…Subdivisions of the germinal subpallium are still not fully established. It has been proposed that a number of subdivisions up to 17 subregions can be differentiated at the transcriptomic level in mice (Flames et al, 2007). …”