Fgfr2 is required for the expansion of the early adrenocortical primordium. (15th September 2015)

• Record Type: Journal Article
• Authors: Häfner, Regine; Bohnenpoll, Tobias; Rudat, Carsten; Schultheiss, Thomas M.; Kispert, Andreas
• Is Part Of: Molecular and cellular endocrinology. Volume 413(2015)
• Page Start: 168
• Page End: 177
• Publication Date: 2015-09-15
• Subjects: Adrenocortical primordium -- Proliferation -- Coelomic epithelium -- Conditional knockout -- Tbx18 -- Fgfr2; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2015.06.022
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: The adrenal cortex is a critical steroidogenic endocrine tissue, generated at least in part from intermediate mesoderm of the anterior urogenital ridge. Previous work has pinpointed a minor role of the FGFR2IIIb isoform in expansion and differentiation of the fetal adrenal cortex in mice but did not address the complete role of FGFR2 and FGFR1 signaling in adrenocortical development. Here, we show that a Tbx18 cre line mediates specific recombination in the coelomic epithelium of the anterior urogenital ridge which gives rise by a delamination process to the adrenocortical primordium. Mice with conditional ( Tbx18 cre -mediated) deletion of all isoforms of Fgfr2 exhibited severely hypoplastic adrenal glands around birth. Cortical cells were dramatically reduced in number but showed steroidogenic differentiation and zonation. Neuroendocrine chromaffin cells were also reduced and formed a cell cluster adjacent to but not encapsulated by steroidogenic cells. Analysis of earlier time points revealed that the adrenocortical primordium was established in the intermediate mesoderm at E10.5 but that it failed to expand at subsequent stages. Our further experiments show that FGFR2 signaling acts as early as E11.5 to prevent apoptosis and enhance proliferation in adrenocortical progenitor cells. FGFR1 signaling does not contribute to early adrenocortical development. Our work suggests that FGFR2IIIb and IIIc isoforms largely act redundantly to promote expansion of the adrenocortical primordium. Highlights: Tbx18 cre is a suitable tool to analyze the molecular control of adrenocortical development. Fgfr2 is expressed in the early adrenocortical primordium. Fgfr2 is required for expansion of the adrenocortical primordium in the urogenital ridge. FGFR2 signaling maintains proliferation and inhibits apoptosis of adrenocortical progenitors. FGFR2 isoforms IIIb and IIIc may act redundantly in adrenocortical development.