Intercellular growth factor signaling and the development of mouse tracheal submucosal glands.
To provide a genetic framework for investigating changes in airway submucosal gland function in human respiratory disease, we have investigated their counterparts in normal and mutant mice. We describe their morphogenesis in relation to the expression of genes encoding conserved intercellular signaling pathways. Submucosal glands are severely reduced in number and size in mice heterozygous for Fgf10. Glands are completely absent in mice lacking Ectodysplasin (Eda) and Edaradd (Eda receptor adaptor protein), members of the tumor necrosis (TNF) superfamily of signaling factors. Furthermore, components of the Eda and closely related pathways are transcribed throughout the respiratory system in the adult mouse. Finally, the temporal and spatial pattern of Bmp4 expression suggests that it may control submucosal gland development and homeostasis. Taken together, our observations have important implications for the better understanding of the submucosal gland remodeling that occurs in human respiratory disease.
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Emma L
EL
Rawlins
Brigid L M
BL
Hogan
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D053331:Ectodysplasins; D053362:Edar-Associated Death Domain Protein; D005110:Extracellular Space / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D008168:Lung / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D020545:Respiratory Mucosa / Q000196:embryology* / Q000254:growth & development / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014132:Trachea / Q000196:embryology* / Q000254:growth & development / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C506018:EDA protein, human; C506125:EDARADD protein, human; D053331:Ectodysplasins; C506019:Eda protein, mouse; D053362:Edar-Associated Death Domain Protein; C506124:Edaradd protein, mouse; D006133:Growth Substances; D008565:Membrane Proteins