Spatial distribution of beta-klotho mRNA in the mouse hypothalamus, hippocampal region, subiculum, and amygdala

Beta-klotho (KLB) is a coreceptor required for endocrine fibroblast growth factor (FGF) 15/19 and FGF21 signaling in the brain. Klb is prominent within the hypothalamus, which is consistent with its metabolic functions, but diverse roles for Klb are now emerging. Central Klb expression is low but discrete and may govern FGF-targeted sites. However, given its low expression, it is unclear if Klb mRNA is more widespread. We performed in situ hybridization to label Klb mRNA to generate spatial maps capturing the distribution and levels of Klb within the mouse hypothalamus, hippocampal region, subiculum, and amygdala. Semiquantitative analysis revealed that Klb-labeled cells may express low, medium, or high levels of Klb mRNA. Hypothalamic Klb hybridization was heterogeneous and varied rostrocaudally within the same region. Most Klb-labeled cells were found in the lateral hypothalamic zone, but the periventricular hypothalamic region, including the suprachiasmatic nucleus, contained the greatest proportion of cells expressing medium or high Klb levels. We also found heterogeneous Klb hybridization in the amygdala and subiculum, where Klb was especially distinct within the central amygdalar nucleus and ventral subiculum, respectively. By contrast, Klb-labeled cells in the hippocampal region only expressed low levels of Klb and were typically found in the pyramidal layer of Ammon's horn or dentate gyrus. The Klb-labeled regions identified in this study are consistent with reported roles of Klb in metabolism, taste preference, and neuroprotection. However, additional identified sites, including within the hypothalamus and amygdala, may suggest novel roles for FGF15/19 or FGF21 signaling.

Automated summary

This study used in situ hybridization to label Klb mRNA and captured the distribution and levels of Klb in the mouse hypothalamus, hippocampal region, subiculum, and amygdala. The results showed heterogeneous expression of Klb in the hypothalamus and amygdala, suggesting novel roles for FGF15/19 or FGF21 signaling. These findings are consistent with the reported functions of Klb in metabolism, taste preference, and neuroprotection.