title: The ets-domain transcription factor Spdef promotes maturation of goblet and paneth cells in the intestinal epithelium.
abstract: OBJECTIVE
  Stem cells within the intestinal epithelium generate daughter cells that undergo lineage commitment and maturation through the combined action of the Wnt and Notch signaling cascades. Both pathways, in turn, regulate transcription factor networks that further define differentiation toward either enterocytes or 1 of 3 secretory cell lineages (Paneth, goblet, or enteroendocrine cells). In this study, we investigated the role of the Wnt-responsive, Ets-domain transcription factor Spdef in the differentiation of goblet and Paneth cells.
  
  
  METHODS
  The in vivo function of Spdef was examined by disrupting the Spdef gene in mice (Spdef(-/-) mice) and analyzing the intestinal phenotype using a range of histologic techniques and DNA microarray profiling.
  
  
  RESULTS
  In accordance with expression data, we found that loss of Spdef severely impaired the maturation of goblet and Paneth cells and, conversely, led to an accumulation of immature secretory progenitors. Spdef appears to positively and negatively regulate a specific subset of goblet and Paneth cell genes, including Cryptdins, Mmp7, Ang4, Kallikreins, and Muc2.
  
  
  CONCLUSIONS
  Spdef acts downstream of Math1 to promote terminal differentiation of a secretory progenitor pool into Paneth and goblet cells.
authors: Hubrecht Institute, Utrecht, The Netherlands.
authors: Alex
authors: A
authors: Gregorieff
authors: Daniel E
authors: DE
authors: Stange
authors: Pekka
authors: P
authors: Kujala
authors: Harry
authors: H
authors: Begthel
authors: Maaike
authors: M
authors: van den Born
authors: Jeroen
authors: J
authors: Korving
authors: Peter J
authors: PJ
authors: Peters
authors: Hans
authors: H
authors: Clevers
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D003106:Colon / Q000378:metabolism* / Q000648:ultrastructure; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D005838:Genotype; D020397:Goblet Cells / Q000378:metabolism* / Q000648:ultrastructure; D007421:Intestine, Small / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D019879:Paneth Cells / Q000378:metabolism* / Q000648:ultrastructure; D010641:Phenotype; D050783:Proto-Oncogene Proteins c-ets / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism* / Q000648:ultrastructure; D014158:Transcription, Genetic
chemical_list: D015415:Biomarkers; D050783:Proto-Oncogene Proteins c-ets; C519908:Spdef protein, mouse