Emx1-Lineage Progenitors Differentially Contribute to Neural Diversity in the Striatum and Amygdala

Abstract

In the developing mammalian basal telencephalon, neural progenitors from the subpallium generate the majority of inhibitory medium spiny neurons (MSNs) in the striatum, while both pallial- and subpallial-derived progenitors contribute to excitatory and inhibitory neuronal diversity in the amygdala. Using a combination of approaches, including genetic fate mapping, cell birth dating, cell migration assays, and electrophysiology, we find that cells derived from the Emx1 lineage contribute to two distinct neuronal populations in the mature basal forebrain: inhibitory MSNs in the striatum and functionally distinct subclasses of excitatory neurons in the amygdala. Our cell birth-dating studies reveal that these two populations are born at different times during early neurogenesis, with the amygdala population born before the MSNs. In the striatum, Emx1-lineage neurons represent a unique subpopulation of MSNs: they are disproportionately localized to the dorsal striatum, are found in dopamine receiving, reelin-positive patches, and are born throughout striatal neurogenesis. In addition, our data suggest that a subpopulation of these Emx1-lineage cells originate in the pallium and subsequently migrate to the developing striatum and amygdala. Our intersectional fate-mapping analysis further reveals that Emx1-lineage cells that coexpress Dlx exclusively generate MSNs but do not contribute to the excitatory neurons in the amygdala. Thus, both the timing of neurogenesis and differential combinatorial gene expression appear to be key determinants of striatal versus amygdala fate decisions of Emx1-lineage cells.

Transcription factors COUP-TFI and COUP-TFII are required for the production of granule cells in the mouse olfactory bulb

“…5F-J We have also deleted COUP-TF alleles in SVZ cells using Emx1-Cre mice (Gorski et al, 2002;Bovetti et al, 2013). Emx1 and Emx1-cre are not only expressed in almost all progenitors in neocortical and septal VZ/SVZ (Gorski et al, 2002), but are also expressed in a large number of progenitors in the LGE and CGE (Cocas et al, 2009;Waclaw et al, 2009 Fig. S10K,L).…”

Adult neural stem cells: plastic or restricted neuronal fates?

“…The migration of progenitors from ventral to dorsal germinative zones (Fishell et al, 1993), as well as in the dorsal to ventral direction (Willaime-Morawek et al, 2006;Cocas et al, 2009), could also contribute to the switch in the generation of neuronal subtypes in the embryonic telencephalon. Cocas et al (Cocas et al, 2009), for example, showed that Emx1-derived cells migrating from dorsal to ventral telencephalon contribute inhibitory medium spiny neurons in the striatum.…”

“…Cocas et al (Cocas et al, 2009), for example, showed that Emx1-derived cells migrating from dorsal to ventral telencephalon contribute inhibitory medium spiny neurons in the striatum. Therefore, neurotransmitter specification in the embryonic telencephalon seems to be a sum of early positional, intrinsic, information and the extrinsic signals coming from the actual environment.…”

Amygdala Regulation of Fear and Emotionality in Fragile X Syndrome

“…Although embryonic development of the amygdala is poorly understood, a wide array of approaches used in a number of studies, including fate mapping, migration assays and genetic knockout studies, are assembling an interesting picture specifically regarding the development of the fear circuits in the amygdala [141,142,143,144]. Several transcription factors and genes are thought to be involved in regulating amygdala development and function, so any disruption of the function of one or more of these genes during development might impair the appropriate functional ensembles of neurons and synapses, which ultimately mediate fear and anxiety behaviors.…”