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- W2018784356 abstract "During mammary gland development, an epithelial bud undergoes branching morphogenesis to expand into a continuous tree-like network of branched ducts [1Hennighausen L. Robinson G.W. Information networks in the mammary gland.Nat. Rev. Mol. Cell Biol. 2005; 6: 715-725Crossref PubMed Scopus (352) Google Scholar]. The process involves multiple cell types that are coordinated by hormones and growth factors coupled with signaling events including Wnt and Hedgehog [2Sternlicht M.D. Kouros-Mehr H. Lu P. Werb Z. Hormonal and local control of mammary branching morphogenesis.Differentiation. 2006; 74: 365-381Crossref PubMed Scopus (213) Google Scholar, 3Brennan K.R. Brown A.M. Wnt proteins in mammary development and cancer.J. Mammary Gland Biol. Neoplasia. 2004; 9: 119-131Crossref PubMed Scopus (197) Google Scholar, 4Lewis M.T. Veltmaat J.M. Next stop, the twilight zone: Hedgehog network regulation of mammary gland development.J. Mammary Gland Biol. Neoplasia. 2004; 9: 165-181Crossref PubMed Scopus (49) Google Scholar, 5Ghajar C.M. Bissell M.J. Extracellular matrix control of mammary gland morphogenesis and tumorigenesis: Insights from imaging.Histochem. Cell Biol. 2008; 130: 1105-1118Crossref PubMed Scopus (100) Google Scholar]. Primary cilia play key roles in the development of many organs by coordinating extracellular signaling (of Wnt and Hedgehog) with cellular physiology [6Haycraft C.J. Banizs B. Aydin-Son Y. Zhang Q. Michaud E.J. Yoder B.K. Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function.PLoS Genet. 2005; 1: e53Crossref PubMed Scopus (629) Google Scholar, 7Corbit K.C. Aanstad P. Singla V. Norman A.R. Stainier D.Y. Reiter J.F. Vertebrate Smoothened functions at the primary cilium.Nature. 2005; 437: 1018-1021Crossref PubMed Scopus (1004) Google Scholar, 8Simons M. Gloy J. Ganner A. Bullerkotte A. Bashkurov M. Krönig C. Schermer B. Benzing T. Cabello O.A. Jenny A. et al.Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways.Nat. Genet. 2005; 37: 537-543Crossref PubMed Scopus (573) Google Scholar]. During mammary development, we find cilia on luminal epithelial, myoepithelial, and stromal cells during early branching morphogenesis when epithelial ducts extend into the fat pad and undergo branching morphogenesis. When branching is complete, cilia disappear from luminal epithelial cells but remain on myoepithelial and stromal cells. Ciliary dysfunction caused by intraflagellar transport defects results in branching defects. These include decreased ductal extension and decreased secondary and tertiary branching, along with reduced lobular-alveolar development during pregnancy and lactation. We find increased canonical Wnt and decreased Hedgehog signaling in the mutant glands, which is consistent with the role of cilia in regulating these pathways [6Haycraft C.J. Banizs B. Aydin-Son Y. Zhang Q. Michaud E.J. Yoder B.K. Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function.PLoS Genet. 2005; 1: e53Crossref PubMed Scopus (629) Google Scholar, 7Corbit K.C. Aanstad P. Singla V. Norman A.R. Stainier D.Y. Reiter J.F. Vertebrate Smoothened functions at the primary cilium.Nature. 2005; 437: 1018-1021Crossref PubMed Scopus (1004) Google Scholar, 8Simons M. Gloy J. Ganner A. Bullerkotte A. Bashkurov M. Krönig C. Schermer B. Benzing T. Cabello O.A. Jenny A. et al.Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways.Nat. Genet. 2005; 37: 537-543Crossref PubMed Scopus (573) Google Scholar, 9Corbit K.C. Shyer A.E. Dowdle W.E. Gaulden J. Singla V. Chen M.H. Chuang P.T. Reiter J.F. Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms.Nat. 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Miller L.A. Smith A.N. Dufort D. Lang R.A. Niswander L.A. Canonical Wnt signaling negatively regulates branching morphogenesis of the lung and lacrimal gland.Dev. Biol. 2005; 286: 270-286Crossref PubMed Scopus (80) Google Scholar] and decreased Hedgehog [15Pepicelli C.V. Lewis P.M. McMahon A.P. Sonic hedgehog regulates branching morphogenesis in the mammalian lung.Curr. Biol. 1998; 8: 1083-1086Abstract Full Text Full Text PDF PubMed Scopus (491) Google Scholar, 16Jaskoll T. Leo T. Witcher D. Ormestad M. Astorga J. Bringas Jr., P. Carlsson P. Melnick M. Sonic hedgehog signaling plays an essential role during embryonic salivary gland epithelial branching morphogenesis.Dev. Dyn. 2004; 229: 722-732Crossref PubMed Scopus (79) Google Scholar] signaling decrease branching morphogenesis, suggesting that Wnt and Hedgehog signaling connect ciliary dysfunction to branching defects." @default.
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- W2018784356 title "Primary Cilia Regulate Branching Morphogenesis during Mammary Gland Development" @default.
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