Moxd1 Is a Marker for Sexual Dimorphism in the Medial Preoptic Area, Bed Nucleus of the Stria Terminalis and Medial Amygdala

Abstract

The brain shows various sex differences in its structures. Various mammalian species exhibit sex differences in the sexually dimorphic nucleus of the preoptic area (SDN-POA) and parts of the extended amygdala such as the principal nucleus of the bed nucleus of the stria terminalis (BNSTpr) and posterodorsal part of the medial amygdala (MePD). The SDN-POA and BNSTpr are male-biased sexually dimorphic nuclei, and characterized by the expression of calbindin D-28K (calbindin 1). However, calbindin-immunoreactive cells are not restricted to the SDN-POA, but widely distributed outside of the SDN-POA. To find genes that are more specific to sexually dimorphic nuclei, we selected candidate genes by searching the Allen brain atlas and examined the detailed expressions of the candidate genes using in situ hybridization. We found that the strong expression of monooxygenase DBH-like 1 (Moxd1) was restricted to the SDN-POA, BNSTpr and MePD. The numbers of Moxd1-positive cells in the SDN-POA, BNSTpr and MePD in male mice were larger than those in female mice. Most of the Moxd1-positive cells in the SDN-POA and BNSTpr expressed calbindin. Neonatal castration of male mice reduced the number of Moxd1-positive cells in the SDN-POA, whereas gonadectomy in adulthood did not change the expression of the Moxd1 gene in the SDN-POA in both sexes. These results suggest that the Moxd1 gene is a suitable marker for sexual dimorphic nuclei in the POA, BNST and amygdala, which enables us to manipulate sexually dimorphic neurons to examine their roles in sex-biased physiology and behaviors.

Multimodal Analysis of Cell Types in a Hypothalamic Node Controlling Social Behavior

“…One of these seven clusters, which expressed higher levels of Esr1 than the others, was female specific (Tsix_Esr1 CCA3 Figures 6B, 6C [this cluster was split into two subclusters by SMART-seq], and S7G). Conversely, clusters Esr1_1 CCA4 and Esr1_2/3 CCA5 ( Figures 6B and 6C) were strongly enriched in males; the latter expressed Moxd1 (Figure 6B), which encodes an enzyme expressed dimorphically in the male hypothalamus (Tsuneoka et al, 2017). To validate these results, we performed seqFISH analysis for additional markers identified by scRNA-seq in males and females using Esr1/Gpc3 or Gldn as reference markers ( Figures 6B and 6F).…”

Integrative inference of brain cell similarities and differences from single-cell genomics

“…A single factor (factor 1) loads strongly on the BNSTpr_Esr2 cluster; among the top dimorphic genes for this factor are Xist, Eif2s3y, Uty, and Greb1, one of the 12 previously validated dimorphic genes (Xu et al, 2012). The top loading genes on the shared component of this factor represent cell-type markers, including Moxd1, a recently validated marker of BNSTpr (Tsuneoka et al, 2017). Greb1 itself also loads highly on the shared component of factor 1, reflecting the fact that Greb1 is a cell-type marker (restricted to the BNSTpr) in both sexes, in addition to showing dimorphic expression.…”

Inhibitory transmission in the bed nucleus of the stria terminalis in male and female mice following morphine withdrawal

“…The bed nucleus of the stria terminalis (BNST), a component of the extended amygdala, is a highly sexually dimorphic forebrain structure mainly composed of gamma‐aminobutyric acid (GABA) neurons. The BNST functions as a critical relay center to regulate a range of emotional and motivational processes, via afferents from cortical and limbic structures and via reciprocal projections with several limbic and hindbrain nuclei .…”