Embryonic transcription factor expression in mice predicts medial amygdala neuronal identity and sex-specific responses to innate behavioral cues

Abstract

The medial subnucleus of the amygdala (MeA) plays a central role in processing sensory cues required for innate behaviors. However, whether there is a link between developmental programs and the emergence of inborn behaviors remains unknown. Our previous studies revealed that the telencephalic preoptic area (POA) embryonic niche is a novel source of MeA destined progenitors. Here, we show that the POA is comprised of distinct progenitor pools complementarily marked by the transcription factors Dbx1 and Foxp2. As determined by molecular and electrophysiological criteria this embryonic parcellation predicts postnatal MeA inhibitory neuronal subtype identity. We further find that Dbx1-derived and Foxp2+ cells in the MeA are differentially activated in response to innate behavioral cues in a sex-specific manner. Thus, developmental transcription factor expression is predictive of MeA neuronal identity and sex-specific neuronal responses, providing a potential developmental logic for how innate behaviors could be processed by different MeA neuronal subtypes.DOI: http://dx.doi.org/10.7554/eLife.21012.001

Sex Differences in Biophysical Signatures across Molecularly Defined Medial Amygdala Neuronal Subpopulations

“…We previously revealed that the embryonically expressed transcription factors, Dbx1 and Foxp2, define different embryonic progenitor pools that are destined to generate two molecularly and electrophysiologically distinct subclasses of mature MeA inhibitory output neurons. We have further shown that MeA Dbx1-lineage and Foxp2-lineage neurons respond in a sex and lineage-specific manner to aggressive, defensive, or mating cues (Lischinsky et al, 2017). Understanding both sex and lineage-specific differences in neuronal biophysical properties is a critical step to ultimately understand how different neuronal populations in the male and female MeA processes sensory information for appropriate behavioral outputs.…”

“…The medial amygdala (MeA) is a major brain nucleus for distinguishing olfactory cues that drive innate behaviors such as mating, territorial defense, predator avoidance and maternal and paternal care (McCarthy and Arnold, 2011;Sokolowski and Corbin, 2012;Bergan et al, 2014;Yang and Shah, 2014;Li and Dulac, 2018). In both females and males, the MeA responds to both sex-specific (e.g., opposite sex odors) and non-sex-specific (e.g., predator odor) cues (Choi et al, 2005;Wu et al, 2009;Root et al, 2014;Carvalho et al, 2015;Unger et al, 2015;Bayless and Shah, 2016;Lischinsky et al, 2017;Yao et al, 2017). In addition, MeA neurons in females and males display differences in a number of anatomic, morphologic, and molecular characteristics, including cell number, dendritic complexity, and gene expression patterns (Cooke et al, 1999;Cooke and Woolley, 2005;Johnson et al, 2008;Morris et al, 2008;Wu et al, 2009Wu et al, , 2017Unger et al, 2015;Chen et al, 2019;Gegenhuber and Tollkuhn, 2019).…”

“…The MeA is comprised of a large variety of neurons, which include diverse subclasses of interneurons and both inhibitory and excitatory projection neurons (Bian, 2013;Keshavarzi et al, 2014;Hashikawa et al, 2018;Canteras et al, 2019;Chen et al, 2019). Although a full cataloging of MeA neuronal diversity remains incomplete, we have previously leveraged embryonic transcription factor expression patterns as a means to classify adult MeA neuronal diversity (Hirata et al, 2009;Carney et al, 2010;Lischinsky et al, 2017). We previously revealed that the embryonically expressed transcription factors, Dbx1 and Foxp2, define different embryonic progenitor pools that are destined to generate two molecularly and electrophysiologically distinct subclasses of mature MeA inhibitory output neurons.…”

The untold stories of the speech gene, the FOXP2 cancer gene

“…Among these, complexes including FOXP2 with nuclear receptors might be promising therapeutic candidates. For instance estrogen and androgen receptors colocalize with Foxp2 in mouse amygdala [ 104 ], and rat brain [ 105 ]. Whether this co-localization translates into real complexes remains unclear.…”

“…Further functional links between FOXP2 and cancer through dysregulation of other signaling processes may warrant examination. Among those we speculate that estrogen/androgen pathways relate FOXP2 and oncogenesis [ 104 , 105 ] (see section 5.1.5 . Prostate cancer).…”