NR5A1 and cell population heterogeneity: Insights into developmental and functional disparities and regulatory mechanisms.

Abstract

Background: NR5A1 plays essential roles in the development of various tissues, including the ventromedial hypothalamus, pituitary gonadotrope, adrenal cortex, spleen, testis, and ovary. Additionally, NR5A1-positive cells in these tissues exhibit developmental and functional heterogeneity.

Methods: This review summarizes recent knowledge on the relationships between physiological functions and gene cascades regulated by NR5A1 in each tissue. In addition, we also present several intriguing examples of disparities in Nr5a1 gene regulation within the same tissues, which are relevant to developmentally and functionally heterogeneous cell populations.

Main findings: The adrenal cortex and testicular Leydig cells exhibit clear biphasic developmental processes, resulting in functionally distinct fetal and adult cell populations in which Nr5a1 is regulated by distinct enhancers. Similar heterogeneity of cell populations has been suggested in other tissues. However, functional differences in each cell population remain unclear, and Nr5a1 gene regulation disparities have not been reported.

Conclusion: Some steroidogenic tissues demonstrate biphasic development, with fetal and adult cell populations playing distinct and crucial physiological roles. Nr5a1 regulation varies across cell populations, and analyses of gene cascades centered on NR5A1 will aid in understanding the mechanisms underlying the development and maturation of reproductive capabilities.