FGF signalling through Fgfr2 isoform IIIb regulates adrenal cortex development

► The adrenal glands from fgfr2IIIb knock-out mice are hypoplastic. ► Steroidogenic enzymes are reduced in fgfr2IIIb knock-out mice. ► Dlk1, rather than Shh, signalling is affected in the adrenal cortex of fgfr2IIIb knock-out mice. ► FGF1 is proposed as the ligand for FGFR2IIIb in the adrenal cortex. Developmental signalling pathways are implicated in the formation and maintenance of the adrenal gland, but their roles are currently not well defined. In recent years it has emerged that Sonic hedgehog (Shh) and Wnt/β catenin signalling are crucial for the growth and development of the adrenal cortex. Here we demonstrate that Fibroblast growth factor receptor (Fgfr) 2 isoforms IIIb and IIIc are expressed mainly in the adrenal subcapsule during embryogenesis and that specific deletion of the Fgfr2 IIIb isoform impairs adrenal development, causing reduced adrenal growth and impaired expression of SF1 and steroidogenic enzymes. The hypoplastic adrenals also have thicker, disorganised capsules which retain Gli1 expression but no longer express Dlk1. Fgfr2 ligands were detected in both the capsule and the cortex, suggesting the importance of signalling between the capsule and the cortex in adrenal development.