Title: Sympathetic Innervation of Brown Adipose Tissue - a Platform to Uncover Fundamental Principles of Developmental Programming
Description: Development of the sympathetic nervous system (SNS) tone onto peripheral organs has been shown to be susceptible to a wide range of external factors, such as temperature. Although it was initially postulated that the sympathetic signal is uniform across the body, there is growing evidence that there can be target-specific sympathetic signals. To date, evidence for a relationship between developmental influences on SNS tone and organ function is purely correlational. An obstacle to investigating the programming of SNS permanently altering physiology is that experimental manipulations of SNS activity during development would impact multiple organ functions simultaneously, which could affect the overall health of the animal and therefore confound interpretation of the results. Here we used brown adipose tissue (BAT) as a platform to define a critical period and identify molecules that contribute to the development of SNS outflow to peripheral organs. In addition, we explored the molecular target-specificity of sympathetic neurons by performing a single-cell RNA sequencing transcriptomic analysis of adult mouse stellate ganglion (SG) in conjunction with retrograde tracing from two of its targets, brown adipose tissue and forelimb.

We discovered four molecularly distinct populations of SG neurons that express unique combinations of neuropeptides and receptors, but we did not find evidence of target specificity. The four distinct SG neuronal populations had marker genes that showed unique expression in each population, including genes encoding secreted peptides and receptors of circulating factors. Also, we found that the expression of some of the marker genes differs across the sympathetic chain, which could provide a means for coordinated regulation of SNS responses to specific types of homeostatic challenges.