Sonic hedgehogexpressing and responding cells generate neuronal diversity in the medial amygdala

Abstract

BackgroundThe mammalian amygdala is composed of two primary functional subdivisions, classified according to whether the major output projection of each nucleus is excitatory or inhibitory. The posterior dorsal and ventral subdivisions of the medial amygdala, which primarily contain inhibitory output neurons, modulate specific aspects of innate socio-sexual and aggressive behaviors. However, the development of the neuronal diversity of this complex and important structure remains to be fully elucidated.ResultsUsing a combination of genetic fate-mapping and loss-of-function analyses, we examined the contribution and function of Sonic hedgehog (Shh)-expressing and Shh-responsive (Nkx2-1+ and Gli1+) neurons in the medial amygdala. Specifically, we found that Shh- and Nkx2-1-lineage cells contribute differentially to the dorsal and ventral subdivisions of the postnatal medial amygdala. These Shh- and Nkx2-1-lineage neurons express overlapping and non-overlapping inhibitory neuronal markers, such as Calbindin, FoxP2, nNOS and Somatostatin, revealing diverse fate contributions in discrete medial amygdala nuclear subdivisions. Electrophysiological analysis of the Shh-derived neurons additionally reveals an important functional diversity within this lineage in the medial amygdala. Moreover, inducible Gli1CreER(T2) temporal fate mapping shows that early-generated progenitors that respond to Shh signaling also contribute to medial amygdala neuronal diversity. Lastly, analysis of Nkx2-1 mutant mice demonstrates a genetic requirement for Nkx2-1 in inhibitory neuronal specification in the medial amygdala distinct from the requirement for Nkx2-1 in cerebral cortical development.ConclusionsTaken together, these data reveal a differential contribution of Shh-expressing and Shh-responding cells to medial amygdala neuronal diversity as well as the function of Nkx2-1 in the development of this important limbic system structure.

Sonic Hedgehog Is a Novel Tubule-Derived Growth Factor for Interstitial Fibroblasts after Kidney Injury

“…As such, Cre is exclusively expressed in Gli1-expressing cells, thereby indicating the target cells of hedgehog signaling in these mice. 28,29 We found that, at 10 days after IRI, Cre was expressed in renal interstitial cells but not tubular cells. Double immunostaining revealed that Cre ( Figure 1J, red) was costained with vimentin (fibroblast marker) ( Figure 1J, green) but not CD45 (common leukocyte marker) or CD31 (endothelial cell marker) ( Figure 1J).…”

Contribution of Genoarchitecture to Understanding Forebrain Evolution and Development, with Particular Emphasis on the Amygdala

“…The only exception is Lhx6 in amphibians since no published data have been found. As noted above, based on these criteria many neurons of the medial amygdala of mammals were proposed to originate either in the pallidal subdivision or the preoptic subdivision [García-López et al, 2008], which was later shown by fate mapping analysis [Hirata et al, 2009;Waclaw et al, 2010;Carney et al, 2010;Bupesh et al, 2011a]. The use of these criteria has also helped to support the identification of a 'medial amygdala' in sauropsids Moreno et al, 2010] and amphibians [Moreno et al, 2008a] ( fig.…”

“…2 ) [Flames et al, 2007;García-López et al, 2008] but also shows expression of other transcription factors such as Dbx1 [Hirata et al, 2009]. Based on gene expression profiles, migration assays, and genetic fate maps, the preoptic area has been shown to produce cells for the medial amygdala [García-López et al, 2008;Hirata et al, 2009;Carney et al, 2010;Bupesh et al, 2011a]. It appears that the neurons originate specifically in the commissural preoptic subdivision [Bupesh et al, 2011a] and that neurons reach primarily the anterior and posteroventral amygdala, where Shh-expressing and Dbx1-lineage cells are principally found ( fig.…”

Embryonic Origin of the Islet1 and Pax6 Neurons of the Chicken Central Extended Amygdala Using Cell Migration Assays and Relation to Different Neuropeptide-Containing Cells

“…In recent years, the embryonic commissural PO, characterized by expression of Nkx2.1, Shh and Lhx7 at the ventricular zone and mantle, has emerged as a major source of neurons for the medial extended amygdala (mouse: García-López et al [2008], Carney et al [2010] and Bupesh et al [2011b] and chicken: Me-dina [2008, 2009] and reviews by Medina et al [2011] and Abellán et al [2013]). More recently, the embryonic commissural PO was also shown to produce a minor subpopulation of catecholaminergic neurons for the EAce and St in mice [Bupesh et al, 2014], and a similar contribution was also suggested to occur in chicken ( fig.…”