Mesenchymal Hox6 function is required for mouse pancreatic endocrine cell differentiation.
Despite significant advances in our understanding of pancreatic endocrine cell development, the function of the pancreatic mesodermal niche in this process is poorly understood. Here we report a novel role for mouse Hox6 genes in pancreatic organogenesis. Hox6 genes are expressed exclusively in the mesoderm of the developing pancreas. Genetic loss of all three Hox6 paralogs (Hoxa6, Hoxb6 and Hoxc6) leads to a dramatic loss of endoderm-derived endocrine cells, including insulin-secreting β-cells, and to mild delays and disruptions in pancreatic branching and exocrine differentiation. Ngn3-expressing pan-endocrine progenitor cells are specified normally in Hox6 mutant pancreata, but fail to mature into hormone-producing cells. Reduced expression of Wnt5a is observed in mutant pancreatic mesenchyme, leading to subsequent loss of expression of the crucial Wnt inhibitors Sfrp3 and Dkk1 in endocrine progenitor cells. These results reveal a key role for Hox6 genes in establishing Wnt mesenchymal-epithelial crosstalk in pancreatic development.
['Larsen|Brian M|BM|', 'Hrycaj|Steven M|SM|', 'Newman|Micaleah|M|', 'Li|Ye|Y|', 'Wellik|Deneen M|DM|']
D000818:Animals D002454:Cell Differentiation D055098:Endocrine Cells D005455:Fluorescent Antibody Technique D018398:Homeodomain Proteins D017403:In Situ Hybridization D008648:Mesoderm D051379:Mice D038081:Organogenesis D010179:Pancreas D060888:Real-Time Polymerase Chain Reaction D013629:Tamoxifen
Mouse Endocrine cells Mesenchymal-epithelial crosstalk Pancreatic development Hox genes Wnt signaling