The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3.
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.
Institute of Biology Valrose, Université de Nice-Sophia, F-06108 Nice, France; UMR1091, Institut National de la Santé et de la Recherche Médicale, F-06108 Nice, France; CNRS, UMR7277, F-06108 Nice, France;
Valerie
V
Vidal
Institute of Biology Valrose, Université de Nice-Sophia, F-06108 Nice, France; UMR1091, Institut National de la Santé et de la Recherche Médicale, F-06108 Nice, France; CNRS, UMR7277, F-06108 Nice, France;
Sonia
S
Sacco
Institute of Biology Valrose, Université de Nice-Sophia, F-06108 Nice, France; UMR1091, Institut National de la Santé et de la Recherche Médicale, F-06108 Nice, France; CNRS, UMR7277, F-06108 Nice, France;
Ana Sofia
AS
Rocha
Institute of Biology Valrose, Université de Nice-Sophia, F-06108 Nice, France; UMR1091, Institut National de la Santé et de la Recherche Médicale, F-06108 Nice, France; CNRS, UMR7277, F-06108 Nice, France;
Fabio
F
da Silva
Institute of Biology Valrose, Université de Nice-Sophia, F-06108 Nice, France; UMR1091, Institut National de la Santé et de la Recherche Médicale, F-06108 Nice, France; CNRS, UMR7277, F-06108 Nice, France;
Clara
C
Panzolini
UMR6293, Centre National de la Recherche Scientifique, Clermont Université, F-63178 Aubière, France; U1103, Institut National de la Santé et de la Recherche Médicale, Clermont Université, F-63178 Aubière, France;
Typhanie
T
Dumontet
Institute of Biology Valrose, Université de Nice-Sophia, F-06108 Nice, France; UMR1091, Institut National de la Santé et de la Recherche Médicale, F-06108 Nice, France; CNRS, UMR7277, F-06108 Nice, France;
Thi Mai Phuong
TM
Doan
Biocenter Oulu, 90220 Oulu, Finland;
Jingdong
J
Shan
Biocenter Oulu, 90220 Oulu, Finland;
Aleksandra
A
Rak-Raszewska
Beatson Institute, Glasgow G61 1BD, United Kingdom.
Tom
T
Bird
Biocenter Oulu, 90220 Oulu, Finland;
Seppo
S
Vainio
UMR6293, Centre National de la Recherche Scientifique, Clermont Université, F-63178 Aubière, France; U1103, Institut National de la Santé et de la Recherche Médicale, Clermont Université, F-63178 Aubière, France;
Antoine
A
Martinez
Institute of Biology Valrose, Université de Nice-Sophia, F-06108 Nice, France; UMR1091, Institut National de la Santé et de la Recherche Médicale, F-06108 Nice, France; CNRS, UMR7277, F-06108 Nice, France;
Andreas
A
Schedl
D000302:Adrenal Cortex / Q000166:cytology / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D004622:Embryo, Mammalian; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D008297:Male; D051379:Mice; D015398:Signal Transduction / Q000235:genetics*; D019699:Thrombospondins / Q000235:genetics / Q000378:metabolism*; D015384:Zona Glomerulosa / Q000166:cytology / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
C517523:R-spondin3 protein, mouse; D019699:Thrombospondins; D051176:beta Catenin
R-spondin signaling; adrenal zonation; mouse models; organ maintenance; β-catenin signaling