title: A network of transcription factors operates during early tooth morphogenesis.
abstract: Improving the knowledge of disease-causing genes is a unique challenge in human health. Although it is known that genes causing similar diseases tend to lie close to one another in a network of protein-protein or functional interactions, the identification of these protein-protein networks is difficult to unravel. Here, we show that Msx1, Snail, Lhx6, Lhx8, Sp3, and Lef1 interact in vitro and in vivo, revealing the existence of a novel context-specific protein network. These proteins are all expressed in the neural crest-derived dental mesenchyme and cause tooth agenesis disorder when mutated in mouse and/or human. We also identified an in vivo direct target for Msx1 function, the cyclin D-dependent kinase (CDK) inhibitor p19(ink4d), whose transcription is differentially modulated by the protein network. Considering the important role of p19(ink4d) as a cell cycle regulator, these results provide evidence for the first time of the unique plasticity of the Msx1-dependent network of proteins in conferring differential transcriptional output and in controlling the cell cycle through the regulation of a cyclin D-dependent kinase inhibitor. Collectively, these data reveal a novel protein network operating in the neural crest-derived dental mesenchyme that is relevant for many other areas of developmental and evolutionary biology.
authors.affiliation: Center for Regenerative Developmental Biology, The Forsyth Institute, Cambridge, Massachusetts, USA.
authors.forename: Minglian
authors.initials: M
authors.lastname: Zhao
authors.forename: Vandana
authors.initials: V
authors.lastname: Gupta
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Raj
authors.forename: Martine
authors.initials: M
authors.lastname: Roussel
authors.forename: Marianna
authors.initials: M
authors.lastname: Bei
mesh_terms: D000818:Animals; D002460:Cell Line; D050764:Cyclin-Dependent Kinase Inhibitor p19 / Q000235:genetics; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000032:analysis / Q000378:metabolism*; D051957:MSX1 Transcription Factor / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D060066:Protein Interaction Maps; D000071250:Snail Family Transcription Factors; D014070:Tooth / Q000254:growth & development* / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: C493975:Cdkn2d protein, mouse; D050764:Cyclin-Dependent Kinase Inhibitor p19; C498504:LHX6 protein, mouse; D060850:LIM-Homeodomain Proteins; D051957:MSX1 Transcription Factor; C484084:Msx1 protein, mouse; D009419:Nerve Tissue Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors