The development of the pancreas, a secretory organ that expands from the endoderm into the surrounding mesoderm-derived mesenchyme, requires a dialogue between its endodermal and mesodermal components. How do these two compartments communicate? To understand the molecular basis of this cellular cross-talk, Deneen Wellik and colleagues (p. 3859) have analysed pancreas organogenesis in mouse, finding that Hox6 genes, a group of patterning genes expressed in the pancreas mesoderm but not in the endoderm, play a crucial role in this process. Indeed, the genetic loss of all Hox6 paralogues results in mild defects in branching and in exocrine differentiation, and a drastic loss of mature endocrine cells. Mechanistically, the authors show that Hox6 depletion results in decreased expression of mesenchymal Wnt5a, a morphogen crucial for pancreas development. This then leads to the loss of the expression of two Wnt inhibitors, Sfrp3 and Dkk1, in endocrine progenitors. Hence, as repression of Wnt signalling in developing endocrine cells is crucial for their differentiation, this study highlights that regional mesodermal patterning cues are essential for the establishment of the mesenchymal/endodermal crosstalk necessary for pancreatic development.
- © 2015. Published by The Company of Biologists Ltd