title: FGF10 is an inducer and Pax6 a competence factor for lacrimal gland development.
abstract: We investigated the mechanism of tissue induction and specification using the lacrimal gland as a model system. This structure begins its morphogenesis as a bud-like outgrowth of the conjunctival epithelium and ultimately forms a branched structure with secretory function. Using a reporter transgene as a specific marker for gland epithelium, we show that the transcription factor Pax6 is required for normal development of the gland and is probably an important competence factor. In investigating the cell-cell signaling required, we show that fibroblast growth factor (FGF) 10 is sufficient to stimulate ectopic lacrimal bud formation in ocular explants. Expression of FGF10 in the mesenchyme adjacent to the presumptive lacrimal bud and absence of lacrimal gland development in FGF10-null mice strongly suggest that it is an endogenous inducer. This was supported by the observation that inhibition of signaling by a receptor for FGF10 (receptor 2 IIIb) suppressed development of the endogenous lacrimal bud. In explants of mesenchyme-free gland epithelium, FGF10 stimulated growth but not branching morphogenesis. This suggested that its role in induction is to stimulate proliferation and, in turn, that FGF10 combines with other factors to provide the instructive signals required for lacrimal gland development.
authors.affiliation: Skirball Institute for Biomolecular Medicine, Developmental Genetics Program, Cell Biology and Pathology Departments, New York University Medical Center, New York, NY 10016, USA.
authors.forename: H P
authors.initials: HP
authors.lastname: Makarenkova
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: V
authors.initials: V
authors.lastname: Govindarajan
authors.forename: S C
authors.initials: SC
authors.lastname: Faber
authors.forename: L
authors.initials: L
authors.lastname: Sun
authors.forename: G
authors.initials: G
authors.lastname: McMahon
authors.forename: P A
authors.initials: PA
authors.lastname: Overbeek
authors.forename: R A
authors.initials: RA
authors.lastname: Lang
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D004848:Epithelium / Q000196:embryology; D005136:Eye Proteins / Q000502:physiology; D051526:Fibroblast Growth Factor 10; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology; D018398:Homeodomain Proteins; D007765:Lacrimal Apparatus / Q000196:embryology*; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D009924:Organ Culture Techniques; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D015398:Signal Transduction
chemical_list: D004268:DNA-Binding Proteins; D005136:Eye Proteins; C496464:Fgf10 protein, mouse; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D016222:Fibroblast Growth Factor 2; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors