The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3

Genes Dev. 2016 Jun 15;30(12):1389-94. doi: 10.1101/gad.277756.116. Epub 2016 Jun 16.


Adrenal glands are zonated endocrine organs that are essential in controlling body homeostasis. How zonation is induced and maintained and how renewal of the adrenal cortex is ensured remain a mystery. Here we show that capsular RSPO3 signals to the underlying steroidogenic compartment to induce β-catenin signaling and imprint glomerulosa cell fate. Deletion of RSPO3 leads to loss of SHH signaling and impaired organ growth. Importantly, Rspo3 function remains essential in adult life to ensure replenishment of lost cells and maintain the properties of the zona glomerulosa. Thus, the adrenal capsule acts as a central signaling center that ensures replacement of damaged cells and is required to maintain zonation throughout life.

Keywords: R-spondin signaling; adrenal zonation; mouse models; organ maintenance; β-catenin signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex / cytology
  • Adrenal Cortex / physiology*
  • Animals
  • Cell Differentiation / genetics*
  • Cell Proliferation
  • Embryo, Mammalian
  • Gene Deletion
  • Gene Expression Regulation, Developmental / genetics
  • Homeostasis / genetics
  • Male
  • Mice
  • Signal Transduction / genetics*
  • Thrombospondins / genetics
  • Thrombospondins / metabolism*
  • Zona Glomerulosa / cytology
  • Zona Glomerulosa / metabolism
  • beta Catenin / metabolism


  • R-spondin3 protein, mouse
  • Thrombospondins
  • beta Catenin