Deconstructing the principles of ductal network formation in the pancreas

TY - JOUR

T1 - Deconstructing the principles of ductal network formation in the pancreas

AU - Dahl-Jensen, Svend Bertel

AU - Yennek, Siham

AU - Flasse, Lydie

AU - Larsen, Hjalte List

AU - Sever, Dror

AU - Karremore, Gopal

AU - Novak, Ivana

AU - Sneppen, Kim

AU - Botton, Anne

PY - 2018/7/26

Y1 - 2018/7/26

N2 - The mammalian pancreas is a branched organ that does not exhibit stereotypic branching patterns, similarly to most other glands. Inside branches, it contains a network of ducts that undergo a transition from unconnected microlumen to a mesh of interconnected ducts and finally to a treelike structure. This ductal remodeling is poorly understood, both on a microscopic and macroscopic level. In this article, we quantify the network properties at different developmental stages. We find that the pancreatic network exhibits stereotypic traits at each stage and that the network properties change with time toward the most economical and optimized delivery of exocrine products into the duodenum. Using in silico modeling, we show how steps of pancreatic network development can be deconstructed into two simple rules likely to be conserved for many other glands. The early stage of the network is explained by noisy, redundant duct connection as new microlumens form. The later transition is attributed to pruning of the network based on the flux of fluid running through the pancreatic network into the duodenum.

AB - The mammalian pancreas is a branched organ that does not exhibit stereotypic branching patterns, similarly to most other glands. Inside branches, it contains a network of ducts that undergo a transition from unconnected microlumen to a mesh of interconnected ducts and finally to a treelike structure. This ductal remodeling is poorly understood, both on a microscopic and macroscopic level. In this article, we quantify the network properties at different developmental stages. We find that the pancreatic network exhibits stereotypic traits at each stage and that the network properties change with time toward the most economical and optimized delivery of exocrine products into the duodenum. Using in silico modeling, we show how steps of pancreatic network development can be deconstructed into two simple rules likely to be conserved for many other glands. The early stage of the network is explained by noisy, redundant duct connection as new microlumens form. The later transition is attributed to pruning of the network based on the flux of fluid running through the pancreatic network into the duodenum.

U2 - 10.1371/journal.pbio.2002842

DO - 10.1371/journal.pbio.2002842

M3 - Journal article

C2 - 30048442

SN - 1544-9173

VL - 16

JO - PLOS Biology

JF - PLOS Biology

IS - 7

M1 - e2002842

ER -