title: Fgfr2 is required for the expansion of the early adrenocortical primordium.
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.
authors.affiliation: Institut für Molekularbiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Regine
authors.initials: R
authors.lastname: Häfner
authors.affiliation: Institut für Molekularbiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bohnenpoll
authors.affiliation: Institut für Molekularbiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Rudat
authors.affiliation: Department of Genetics and Developmental Biology, Rappaport-Technion Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Schultheiss
authors.affiliation: Institut für Molekularbiologie, Medizinische Hochschule Hannover, Hannover, Germany. Electronic address: kispert.andreas@mh-hannover.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kispert
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology / Q000196:embryology*; D000818:Animals; D019439:Chromaffin Cells / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D007527:Isoenzymes; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: Adrenocortical primordium; Coelomic epithelium; Conditional knockout; Fgfr2; Proliferation; Tbx18