Abstract

The amygdala is a hyperspecialized brain region composed of strongly inter- and intraconnected nuclei involved in emotional learning and behavior. The cellular heterogeneity of the amygdalar nuclei has complicated straightforward conclusions on their developmental origin, and even resulted in contradictory data. Recently, the concentric ring theory of the pallium and the radial histogenetic model of the pallial amygdala have cleared up several uncertainties that plagued previous models of amygdalar development. Here, we provide an extensive overview on the developmental origin of the nuclei of the amygdaloid complex. Starting from older gene expression data, transplantation and lineage tracing studies, we systematically summarize and reinterpret previous findings in light of the novel perspectives on amygdalar development. In addition, migratory routes that these cells take on their way to the amygdala are explored, and known transcription factors and guidance cues that seemingly drive these cells toward the amygdala are emphasized. We propose some future directions for research on amygdalar development and highlight that a better understanding of its development could prove critical for the treatment of several neurodevelopmental and neuropsychiatric disorders.

Highlights

  • The amygdaloid complex is a cluster of approximately 13 nuclei that are located in the ventrocaudal telencephalon and are considered a part of the limbic system

  • Older papers often focused on single gene expression patterns to link nuclei to molecularly “similar” progenitor regions, an at the time common approach that resulted in multiple erroneous conclusions

  • This is highlighted by the only recent discovery that the amygdala is not generated in the cortical pallium, but rather contains its own pallial field

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Summary

Introduction

The amygdaloid complex is a cluster of approximately 13 nuclei that are located in the ventrocaudal telencephalon and are considered a part of the limbic system. A combination of gene expression analysis, in utero gene transfer studies and lineage tracing revealed that the majority of projection neurons in the LA and anterior BLA nuclei originate from a Dbx1+ progenitor pool starting from E11.5 (Medina et al, 2004; Bielle et al, 2005; Hirata et al, 2009; Soma et al, 2009; Waclaw et al, 2010; Puelles et al, 2016a).

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