Bone morphogenetic protein signaling is essential for terminal differentiation of the intestinal secretory cell lineage.
OBJECTIVE
Bone morphogenetic proteins (Bmps) are morphogens known to play key roles in gastrointestinal development and pathology. Most Bmps are produced primarily by the mesenchymal compartment and activate their signaling pathways following a paracrine or autocrine route. The aim of this study was to investigate the role of epithelial Bmp signaling in intestinal morphogenesis and maintenance of adult epithelial cell functions.


METHODS
With the use of tissue-specific gene ablation, we generated mice lacking the Bmp receptor type IA (Bmpr1a) exclusively in the intestinal epithelium. Bmpr1a mutant and control mice were sacrificed for histology, immunofluorescence, Western blot analysis, electron microscopy, and quantitative polymerase chain reaction.


RESULTS
As well as showing increased proliferation and altered intestinal epithelial morphology, Bmpr1a mutant mice revealed that epithelial Bmp signaling is associated with impaired terminal differentiation of cells from the secretory lineage but not with the determination of cell fate. Loss of Bmp signaling exclusively in the epithelial compartment is not sufficient for the initiation of the de novo crypt phenomenon associated with juvenile polyposis syndrome.


CONCLUSIONS
Epithelial Bmp signaling plays an important role in the terminal differentiation of the intestinal secretory cell lineage but not in de novo crypt formation. These findings emphasize the importance of delineating the contribution of the stroma vs the epithelium in gastrointestinal physiology and pathology.
Auclair
Benoit A
BA
Canadian Institutes of Health Research Team on Digestive Epithelium, Département d'Anatomie et Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Benoit
Yannick D
YD
Rivard
Nathalie
N
Mishina
Yuji
Y
Perreault
Nathalie
N
D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007583:Jejunum / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology; D051176:beta Catenin / Q000502:physiology
D019485:Bone Morphogenetic Proteins; D051153:Wnt Proteins; D051176:beta Catenin; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I