The ets-domain transcription factor Spdef promotes maturation of goblet and paneth cells in the intestinal epithelium.
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.
Gregorieff
Alex
A
Hubrecht Institute, Utrecht, The Netherlands.
Stange
Daniel E
DE
Kujala
Pekka
P
Begthel
Harry
H
van den Born
Maaike
M
Korving
Jeroen
J
Peters
Peter J
PJ
Clevers
Hans
H
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
D015415:Biomarkers; D050783:Proto-Oncogene Proteins c-ets; C519908:Spdef protein, mouse