title: FGF signalling through Fgfr2 isoform IIIb regulates adrenal cortex development.
abstract: 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.
authors: Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK.
authors: Leonardo
authors: L
authors: Guasti
authors: W C
authors: WC
authors: Candy Sze
authors: Tristan
authors: T
authors: McKay
authors: Richard
authors: R
authors: Grose
authors: Peter J
authors: PJ
authors: King
mesh_terms: D000302:Adrenal Cortex / Q000196:embryology*; D000818:Animals; D002135:Calcium-Binding Proteins; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D054339:Steroidogenic Factor 1 / Q000096:biosynthesis / Q000235:genetics; D000071676:Zinc Finger Protein GLI1
chemical_list: D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; C498520:Gli1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors; D020033:Protein Isoforms; D054339:Steroidogenic Factor 1; D000071676:Zinc Finger Protein GLI1; D005346:Fibroblast Growth Factors; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2
references: Cell. 1994 May 20;77(4):481-90
references: 8187173
references: Endocrinology. 2002 Aug;143(8):3122-35
references: 12130578
references: Dev Cell. 2009 Apr;16(4):607-13
references: 19386269
references: Development. 2008 Aug;135(15):2593-602
references: 18599507
references: Dev Biol. 2001 Mar 1;231(1):47-62
references: 11180951
references: Am J Pathol. 2004 Jun;164(6):2229-40
references: 15161655
references: Genes Cells. 1996 Jul;1(7):663-71
references: 9078392
references: Dev Cell. 2005 Jan;8(1):85-95
references: 15621532
references: Cell. 1993 May 21;73(4):725-34
references: 8500166
references: Cell. 1994 Dec 16;79(6):993-1003
references: 8001146
references: Hepatology. 2007 Oct;46(4):1187-97
references: 17668871
references: J Biol Chem. 2006 Jun 9;281(23):15694-700
references: 16597617
references: Genome Biol. 2001;2(3):REVIEWS3005
references: 11276432
references: PLoS One. 2012;7(11):e50401
references: 23308088
references: Endocr Rev. 2009 May;30(3):241-63
references: 19403887
references: Development. 2006 Jun;133(12):2325-35
references: 16720875
references: Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21185-90
references: 19955443
references: Tissue Eng Part A. 2009 Aug;15(8):2093-101
references: 19196135
references: Mol Cell Endocrinol. 2012 Mar 31;351(1):19-27
references: 22020162
references: Genesis. 2009 Sep;47(9):628-37
references: 19536807
references: Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16558-63
references: 17940049
references: Mech Dev. 2001 Sep;107(1-2):69-82
references: 11520664
references: Endocrinology. 2010 Mar;151(3):1119-28
references: 20118198
references: Endocrinology. 1998 Jul;139(7):3316-28
references: 9645708
references: Genes Dev. 2003 Feb 1;17(3):342-7
references: 12569124
references: Endocrinology. 2005 Jun;146(6):2555-62
references: 15731356
references: Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2973-8
references: 17299056
references: Genesis. 2004 May;39(1):52-7
references: 15124227
references: EMBO J. 2007 Mar 7;26(5):1268-78
references: 17304214
references: Dev Cell. 2009 Apr;16(4):600-6
references: 19386268
references: J Mol Endocrinol. 2004 Dec;33(3):623-38
references: 15591023
references: Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3855-60
references: 11274405
references: Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18205-10
references: 17989225
references: J Clin Endocrinol Metab. 1981 Oct;53(4):790-6
references: 6270174
references: Mol Cell Endocrinol. 2011 Apr 10;336(1-2):117-22
references: 21094676
references: Mol Endocrinol. 2009 Nov;23(11):1717-25
references: 19541743
references: Development. 2000 Feb;127(3):483-92
references: 10631169
references: Nat Rev Cancer. 2010 Feb;10(2):116-29
references: 20094046