title: Transcription factors Runx1 to 3 are expressed in the lacrimal gland epithelium and are involved in regulation of gland morphogenesis and regeneration.
abstract: OBJECTIVE
  Lacrimal gland (LG) morphogenesis and repair are regulated by a complex interplay of intrinsic factors (e.g., transcription factors) and extrinsic signals (e.g., soluble growth/signaling factors). Many of these interconnections remain poorly characterized. Runt-related (Runx) factors belong to a small family of heterodimeric transcription factors known to regulate lineage-specific proliferation and differentiation of stem cells. The purpose of this study was to define the expression pattern and the role of Runx proteins in LG development and regeneration.
  
  
  METHODS
  Expression of epithelial-restricted transcription factors in murine LG was examined using immunostaining, qRT-PCR, and RT(2)Profiler PCR microarrays. The role of Runx transcription factors in LG morphogenesis was studied using siRNA and ex vivo LG cultures. Expression of Runx transcription factors during LG regeneration was assessed using in vivo model of LG regeneration.
  
  
  RESULTS
  We found that Runx factors are expressed in the epithelial compartment of the LG; in particular, Runx1 was restricted to the epithelium with highest level of expression in ductal and centroacinar cells. Downregulation of Runx1 to 3 expression using Runx-specific siRNAs abolished LG growth and branching and our data suggest that Runx1, 2, and 3 are partially redundant in LG development. In siRNA-treated LG, reduction of branching correlated with reduction of epithelial proliferation, as well as expression of cyclin D1 and the putative epithelial progenitor cell marker cytokeratin-5. Runx1, Runx3, and cytokeratin-5 expression increased significantly in regenerating LG and there was modest increase in Runx2 expression during LG differentiation.
  
  
  CONCLUSIONS
  Runx1 and 2 are new markers of the LG epithelial lineage and Runx factors are important for normal LG morphogenesis and regeneration.
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Voronov
authors.forename: Anastasia
authors.initials: A
authors.lastname: Gromova
authors.forename: Daren
authors.initials: D
authors.lastname: Liu
authors.forename: Driss
authors.initials: D
authors.lastname: Zoukhri
authors.forename: Alexander
authors.initials: A
authors.lastname: Medvinsky
authors.forename: Robyn
authors.initials: R
authors.lastname: Meech
authors.forename: Helen P
authors.initials: HP
authors.lastname: Makarenkova
mesh_terms: D000818:Animals; D015415:Biomarkers; D049109:Cell Proliferation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics* / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics* / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D053555:Keratin-5 / Q000235:genetics / Q000378:metabolism; D007765:Lacrimal Apparatus / Q000196:embryology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009024:Morphogenesis / Q000502:physiology*; D009924:Organ Culture Techniques; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration / Q000502:physiology*
chemical_list: D015415:Biomarkers; C530105:Ccnd1 protein, mouse; D050659:Core Binding Factor Alpha 1 Subunit; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D053555:Keratin-5; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C493726:Runx1 protein, mouse; C493716:Runx2 protein, mouse; C493730:Runx3 protein, mouse; D019938:Cyclin D1
keywords: Runx1; Runx2; Runx3; lacrimal gland regeneration; qRT PCR microarrays; stem and progenitor cells