Molecular control of two novel migratory paths for CGE-derived interneurons in the developing mouse brain

Abstract

GABAergic interneurons are highly heterogeneous and originate in the subpallium mainly from the medial (MGE) and caudal (CGE) ganglionic eminences according to a precise temporal sequence. MGE-derived cells disperse dorsally and migrate towards all regions of the cortex, but little is known about how CGE-derived cells reach their targets during development. Here, we unravel the existence of two novel CGE caudo-rostral migratory streams, one located laterally (LMS) and the other one more medially (MMS), that, together with the well-known caudal migratory stream (CMS), contribute to populate the neocortex, hippocampus and amygdala. These paths appear in a precise temporal sequence and express a distinct combination of transcription factors, such as SP8, PROX1, COUP-TFI and COUP-TFII. By inactivating COUP-TFI in developing interneurons, the lateral and medial streams are perturbed and expression of SP8 and COUP-TFII affected. As a consequence, adult mutant neocortices have laminar-specific alterations of distinct cortical interneuron subtypes. Overall, we propose that the existence of spatially and temporally regulated migratory paths in the subpallium contributes to the laminar distribution and specification of distinct interneuron subpopulations in the adult brain.

Transcriptional Architecture of Synaptic Communication Delineates GABAergic Neuron Identity

“…Conditional deletions of several of these TFs in adult cortex result in the loss of markers and physiological properties characteristic to their identity (e.g. (Close et al, 2012; Touzot et al, 2016), suggesting their requirement in mature neurons to maintain aspects of cell phenotypes and identity.…”

Sculpting Cerebral Cortex with Serotonin in Rodent and Primate

“…The ventral and the dorsal parts of the MGE expressing the homeobox transcription factor Lhx6 generate fast-spiking/PV+ and adapting/SOM+ interneurons [81][82][83][84][85]. The CGE, a region that expresses the transcription factor Gsh2, COUP-TFII but lacks the transcription factors Nkx2.1, Nkx6.2 and Lhx6 [80,86,87], generates VIP+, CR+, NPY+ and nNOS+ interneurons [20,52,85,88]. Once produced, interneurons are targeted towards specific brain regions, including cortex, depending on the transcription factors and guidance cues they express [87,89].…”

“…The CGE, a region that expresses the transcription factor Gsh2, COUP-TFII but lacks the transcription factors Nkx2.1, Nkx6.2 and Lhx6 [80,86,87], generates VIP+, CR+, NPY+ and nNOS+ interneurons [20,52,85,88]. Once produced, interneurons are targeted towards specific brain regions, including cortex, depending on the transcription factors and guidance cues they express [87,89]. They initially follow parallel migratory streams, first in the IZ and MZ and later on along the SVZ, before they switch their migratory mode and incorporate into the developing CP through radial migration (see Figure 2B).…”

Primary Cilia Signaling Shapes the Development of Interneuronal Connectivity

“…Disrupted IN circuit formation, homeostasis and the resultant excitatory/inhibitory (E/I) imbalance is a convergent mechanism underlying neurodevelopmental disorders such as autism spectrum disorders (ASD), schizophrenia, and intellectual disabilities (Bourgeron, 2009; Kepecs and Fishell, 2014; Marín, 2012). INs, originating from the ventral telencephalon, migrate widely in different trajectories to populate distinct brain regions and integrate into local neural circuits (Guo and Anton, 2014; Marín, 2013; Touzot et al, 2016). Extensive efforts have been made toward understanding the fate specification and migration of INs (Kepecs and Fishell, 2014; Marín, 2013).…”