title: FGF and EDA pathways control initiation and branching of distinct subsets of developing nasal glands.
abstract: Hypertrophy, hyperplasia and altered mucus secretion from the respiratory submucosal glands (SMG) are characteristics of airway diseases such as cystic fibrosis, asthma and chronic bronchitis. More commonly, hyper-secretion of the nasal SMGs contributes to allergic rhinitis and upper airway infection. Considering the role of these glands in disease states, there is a significant dearth in understanding the molecular signals that regulate SMG development and patterning. Due to the imperative role of FGF signalling during the development of other branched structures, we investigated the role of Fgf10 during initiation and branching morphogenesis of murine nasal SMGs. Fgf10 is expressed in the mesenchyme around developing SMGs while expression of its receptor Fgfr2 is seen within glandular epithelial cells. In the Fgf10 null embryo, Steno's gland and the maxillary sinus gland were completely absent while other neighbouring nasal glands showed normal duct elongation but defective branching. Interestingly, the medial nasal glands were present in Fgf10 homozygotes but missing in Fgfr2b mutants, with expression of Fgf7 specifically expressed around these developing glands, indicating that Fgf7 might compensate for loss of Fgf10 in this group of glands. Intriguingly the lateral nasal glands were only mildly affected by loss of FGF signalling, while these glands were missing in Eda mutant mice, where the Steno's and maxillary sinus gland developed as normal. This analysis reveals that regulation of nasal gland development is complex with different subsets of glands being regulated by different signalling pathways. This analysis helps shed light on the nasal gland defects observed in patients with hypohidrotic ectodermal dysplasia (HED) (defect EDA pathway) and LADD syndrome (defect FGFR2b pathway).
authors: Department of Craniofacial Development and Stem Cell Biology, Guy's Hospital, King's College London, United Kingdom.
authors: Alison J
authors: AJ
authors: May
authors: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom.
authors: Denis
authors: D
authors: Headon
authors: Orthodontics, Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki 00014, Finland; Orthodontics, Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, Helsinki 00290, Finland.
authors: David P
authors: DP
authors: Rice
authors: MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, United Kingdom.
authors: Alistair
authors: A
authors: Noble
authors: Department of Craniofacial Development and Stem Cell Biology, Guy's Hospital, King's College London, United Kingdom. Electronic address: abigail.tucker@kcl.ac.uk.
authors: Abigail S
authors: AS
authors: Tucker
mesh_terms: D000818:Animals; D053331:Ectodysplasins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000069916:Endoscopic Mucosal Resection; D005088:Exocrine Glands / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D051526:Fibroblast Growth Factor 10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051523:Fibroblast Growth Factor 7 / Q000502:physiology; D008297:Male; D008443:Maxillary Sinus / Q000196:embryology / Q000648:ultrastructure; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis; D009297:Nasal Mucosa / Q000196:embryology / Q000648:ultrastructure; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D053331:Ectodysplasins; C506019:Eda protein, mouse; C496464:Fgf10 protein, mouse; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: Branching morphogenesis; EDA; FGF10; Submucosal gland (SMGs)