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Publication : Submandibular gland morphogenesis: stage-specific expression of TGF-alpha/EGF, IGF, TGF-beta, TNF, and IL-6 signal transduction in normal embryonic mice and the phenotypic effects of TGF-beta2, TGF-beta3, and EGF-r null mutations.

First Author  Jaskoll T Year  1999
Journal  Anat Rec Volume  256
Issue  3 Pages  252-68
PubMed ID  10521784 Mgi Jnum  J:69420
Mgi Id  MGI:1934551 Doi  10.1002/(SICI)1097-0185(19991101)256:3<252::AID-AR5>3.0.CO;2-6
Citation  Jaskoll T, et al. (1999) Submandibular gland morphogenesis: stage-specific expression of TGF-alpha/EGF, IGF, TGF-beta, TNF, and IL-6 signal transduction in normal embryonic mice and the phenotypic effects of TGF-beta2, TGF-beta3, and EGF-r null mutations. Anat Rec 256(3):252-68
abstractText  Branching morphogenesis of the mouse submandibular gland (SMG) is dependent on cell-cell conversations between and within epithelium and mesenchyme. Such conversations are typically mediated in other branching organs (lung, mammary glands, etc.) by hormones, growth factors, cytokines, and the like in such a way as to translate endocrine, autocrine, and paracrine signals into specific gene responses regulating cell division, apoptosis, and histodifferentiation. We report here the protein expression in embryonic SMGs of four signal transduction pathways: TGF-alpha/EGF/EGF-R; IGF-II/IGF-IR/IGF-IIR; TGF-betas and cognate receptors; TNF, IL-6, and cognate receptors. Their in vivo spatiotemporal expression is correlated with specific stages of progressive SMG development and particular patterns of cell proliferation, apoptosis, and mucin expression. Functional necessity regarding several of these pathways was assessed in mice with relevant null mutations (TGF-beta2, TGF-beta(3), EGF-R). Among many observations, the following seem of particular importance: (1) TGF-alpha and EGF-R, but not EGF, are found in the Initial and Pseudoglandular Stages of SMG development; (2) ductal and presumptive acini lumena formation was associated with apoptosis and TNF/TNF-R1 signalling; (3) TGF-beta2 and TGF-beta3 null mice have normal SMG phenotypes, suggesting the presence of other pathways of mitostasis; (4) EGF-R null mice displayed an abnormal SMG phenotype consisting of decreased branching. These and other findings provide insight into the design of future functional studies.
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