Developmental Links between the Fetal and Adult Zones of the Adrenal Cortex Revealed by Lineage Tracing

Abstract

The nuclear receptor Ad4BP/SF-1 is essential for development of the adrenal cortex and the gonads, which derive from a common adrenogonadal primordium. The adrenal cortex subsequently forms morphologically distinct compartments: the inner (fetal) and outer (definitive or adult) zones. Despite considerable effort, the mechanisms that mediate the differential development of the adrenal and gonadal primordia and the fetal and adult adrenal cortices remain incompletely understood. We previously identified a fetal adrenal-specific enhancer (FAdE) in the Ad4BP/SF-1 locus that directs transgene expression to the fetal adrenal cortex and demonstrated that this enhancer is autoregulated by Ad4BP/SF-1. We now combine the FAdE with the Cre/loxP system to trace cell lineages in which the FAdE was active at some stage in development. These lineage-tracing studies establish definitively that the adult cortex derives from precursor cells in the fetal cortex in which the FAdE was activated before the organization into two distinct zones. The potential of these fetal adrenocortical cells to enter the pathway that eventuates in cells of the adult cortex disappeared by embryonic day 14.5. Thus, these studies demonstrate a direct link between the fetal and adult cortices involving a transition that must occur before a specific stage of development.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://mcb.asm.org/ .

ACKNOWLEDGMENTS

We thank K. Mihara and M. Sakaguchi (Kyushu University) for providing the anti-β-galactosidase antibody, H. Okano (Keio University) for providing nestin-Hsp68-EGFP, T. Imai and P. Chambon for providing pGS-Cre-ERT2, Isao Matsuo (Kumamoto University) for ROSA26R mice, S. Oka for technical assistance, Etoh Tomoo for helpful suggestions on the generation of the Tg mice, and A. L. Reuter for helpful discussions on the manuscript.

This work was supported in part by grants-in-aid for scientific research on priority areas and a grant-in-aid for scientific research (B) from the Ministry of Education, Culture, Sports Science, and Technology of Japan (to K.-I.M.) and by NIH grants DK54480 and HD046743 (to K.L.P.).