title: Embryonic submandibular gland morphogenesis: stage-specific protein localization of FGFs, BMPs, Pax6 and Pax9 in normal mice and abnormal SMG phenotypes in FgfR2-IIIc(+/Delta), BMP7(-/-) and Pax6(-/-) mice.
abstract: Embryonic submandibular salivary gland (SMG) initiation and branching morphogenesis are dependent on cell-cell communications between and within epithelium and mesenchyme. Such communications are typically mediated in other organs (teeth, lung, lacrimal glands) by growth factors in such a way as to translate autocrine, juxtacrine and paracrine signals into specific gene responses regulating cell division and histodifferentiation. Using Wnt1-Cre/R26R transgenic mice, we demonstrate that embryonic SMG mesenchyme is derived exclusively from cranial neural crest. This origin contrasts to that known for tooth mesenchyme, previously shown to be derived from both neural crest and nonneural crest cells. Thus, although both SMGs and teeth are mandibular derivatives, we can expect overlap and differences in the details of their early inductive interactions. In addition, since embryonic SMG branching morphogenesis is analogous to that seen in other branching organs, we also expect similarities of expression regarding those molecules known to be ubiquitous regulators of morphogenesis. In this study, we performed an analysis of the distribution of specific fibroblast growth factors (FGFs), FGF receptors, bone morphogenetic proteins (BMPs) and Pax transcription factors, previously shown to be important for tooth development and/or branching morphogenesis, from the time of initiation of embryonic SMG development until early branching morphogenesis. In addition, we report abnormal SMG phenotypes in FgfR2- IIIc(+/Delta), BMP7(-/-) and Pax6(-/-) mice. Our results, in comparison with functional studies in other systems, suggest that FGF-2/FGFR-1, FGF-8/FGFR-2(IIIc) and FGF-10/FGFR-2(IIIb) signaling have different paracrine and juxtacrine functions during SMG initial bud formation and branching. Finally, our observations of abnormal SMGs in BMP7(-/-) and Pax6(-/-) indicate that both BMP7 and Pax6 play important roles during embryonic SMG branching morphogenesis.
authors.affiliation: Laboratory for Developmental Genetics, University of Southern California, Los Angeles, CA 90089-0641, USA. tjaskoll@hsc.usc.edu
authors.forename: Tina
authors.initials: T
authors.lastname: Jaskoll
authors.forename: Yan Min
authors.initials: YM
authors.lastname: Zhou
authors.forename: Yang
authors.initials: Y
authors.lastname: Chai
authors.forename: Helen P
authors.initials: HP
authors.lastname: Makarenkova
authors.forename: J Martin
authors.initials: JM
authors.lastname: Collinson
authors.forename: John D
authors.initials: JD
authors.lastname: West
authors.forename: Mohammad K
authors.initials: MK
authors.lastname: Hajihosseini
authors.forename: Jina
authors.initials: J
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Melnick
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000032:analysis*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000032:analysis*; D004848:Epithelium / Q000502:physiology; D005136:Eye Proteins; D005260:Female; D005346:Fibroblast Growth Factors / Q000032:analysis*; D005865:Gestational Age; D018398:Homeodomain Proteins / Q000032:analysis*; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009024:Morphogenesis; D000071841:PAX6 Transcription Factor; D051764:PAX9 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D013363:Submandibular Gland / Q000002:abnormalities / Q000196:embryology*; D014157:Transcription Factors / Q000032:analysis*
chemical_list: D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051764:PAX9 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D005346:Fibroblast Growth Factors