title: FGF signaling activates a Sox9-Sox10 pathway for the formation and branching morphogenesis of mouse ocular glands.
abstract: Murine lacrimal, harderian and meibomian glands develop from the prospective conjunctival and eyelid epithelia and produce secretions that lubricate and protect the ocular surface. Sox9 expression localizes to the presumptive conjunctival epithelium as early as E11.5 and is detected in the lacrimal and harderian glands as they form. Conditional deletion showed that Sox9 is required for the development of the lacrimal and harderian glands and contributes to the formation of the meibomian glands. Sox9 regulates the expression of Sox10 to promote the formation of secretory acinar lobes in the lacrimal gland. Sox9 and FGF signaling were required for the expression of cartilage-associated extracellular matrix components during early stage lacrimal gland development. Fgfr2 deletion in the ocular surface epithelium reduced Sox9 and eliminated Sox10 expression. Sox9 deletion from the ectoderm did not affect Fgf10 expression in the adjacent mesenchyme or Fgfr2 expression in the epithelium, but appeared to reduce FGF signaling. Sox9 heterozygotes showed a haploinsufficient phenotype, in which the exorbital branch of the lacrimal gland was absent in most cases. However, enhancement of epithelial FGF signaling by expression of a constitutively active FGF receptor only partially rescued the lacrimal gland defects in Sox9 heterozygotes, suggesting a crucial role of Sox9, downstream of FGF signaling, in regulating lacrimal gland branching and differentiation.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China Department of Ophthalmology and Visual Sciences, Washington University, St Louis, MO 63130, USA.
authors.forename: Ziyan
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University, St Louis, MO 63130, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University, St Louis, MO 63130, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University, St Louis, MO 63130, USA.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Dattilo
authors.affiliation: Department of Developmental Biology, Washington University, St Louis, MO 63130, USA.
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Huh
authors.affiliation: Department of Developmental Biology, Washington University, St Louis, MO 63130, USA.
authors.forename: David
authors.initials: D
authors.lastname: Ornitz
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University, St Louis, MO 63130, USA Department of Cell Biology and Physiology, Washington University, St Louis, MO 63130, USA beebe@wustl.edu.
authors.forename: David C
authors.initials: DC
authors.lastname: Beebe
mesh_terms: D000818:Animals; D051526:Fibroblast Growth Factor 10 / Q000378:metabolism; D006243:Harderian Gland / Q000196:embryology*; D006652:Histological Techniques; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007765:Lacrimal Apparatus / Q000196:embryology*; D061346:Laser Capture Microdissection; D008537:Meibomian Glands / Q000196:embryology*; D051379:Mice; D046228:Microarray Analysis; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D055758:SOX9 Transcription Factor / Q000378:metabolism*; D055757:SOXE Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D055758:SOX9 Transcription Factor; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; C527933:Sox9 protein, mouse
keywords: FGF signaling; Harderian gland; Lacrimal gland; Sox10; Sox9