Stomach regional specification requires Hoxa5-driven mesenchymal-epithelial signaling.
The genetic control of gut regionalization relies on a hierarchy of molecular events in which the Hox gene family of transcription factors is suspected to be key participant. We have examined the role of Hox genes in gut patterning using the Hoxa5(-/-) mice as a model. Hoxa5 is expressed in a dynamic fashion in the mesenchymal component of the developing gut. Its loss of function results in gastric enzymatic anomalies in Hoxa5(-/-) surviving mutants that are due to perturbed cell specification during stomach development. Histological, biochemical and molecular characterization of the mutant stomach phenotype may be compatible with a homeotic transformation of the gastric mucosa. As the loss of mesenchymal Hoxa5 function leads to gastric epithelial defects, Hoxa5 should exert its action by controlling molecules involved in mesenchymal-epithelial signaling. Indeed, in the absence of Hoxa5 function, the expression of genes encoding for signaling molecules such as sonic hedgehog, Indian hedgehog, transforming growth factor beta family members and fibroblast growth factor 10, is altered. These findings provide insight into the molecular controls of patterning events of the stomach, supporting the notion that Hoxa5 acts in regionalization and specification of the stomach by setting up the proper domains of expression of signaling molecules.
Aubin
Josée
J
Centre de recherche en cancérologie de l'Université Laval, Centre Hospitalier Universitaire de Québec, L'Hôtel-Dieu de Québec, Canada.
Déry
Ugo
U
Lemieux
Margot
M
Chailler
Pierre
P
Jeannotte
Lucie
L
D000818:Animals; D019521:Body Patterning; D003106:Colon / Q000196:embryology / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D010434:Pepsin A / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013270:Stomach / Q000196:embryology*; D014157:Transcription Factors
C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D018398:Homeodomain Proteins; C059637:Hoxa5 protein, mouse; D010750:Phosphoproteins; D014157:Transcription Factors; D005346:Fibroblast Growth Factors; D010434:Pepsin A