Mechanical stretch and PI3K signaling link cell migration and proliferation to coordinate epithelial tubule morphogenesis in the zebrafish pronephros

Organ development leads to the emergence of organ function, which in turn can impact developmental processes. Here we show that fluid flow-induced collective epithelial migration during kidney nephron morphogenesis induces cell stretch that in turn signals epithelial proliferation. Increased cell pr...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2012-07, Vol.7 (7), p.e39992-e39992
Main Authors: Vasilyev, Aleksandr, Liu, Yan, Hellman, Nathan, Pathak, Narendra, Drummond, Iain A
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Animals
Automotive parts
Biology
Biomechanical Phenomena
Cell adhesion & migration
Cell migration
Cell Movement
Cell Proliferation
Computational fluid dynamics
Computer applications
Cyclin D1
Cyclin-dependent kinase 4
Cytology
Danio rerio
Epithelial Cells - cytology
Fluid flow
Kidney Tubules - cytology
Kidney Tubules - embryology
Kinases
Leukocyte migration
Mechanical Phenomena
Models, Biological
Morphogenesis
Phosphatidylinositol 3-Kinases - metabolism
Pronephros - cytology
Pronephros - embryology
Recursive functions
Rodents
Signal Transduction
Signaling
Signals
Zebrafish
Zebrafish - embryology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Organ development leads to the emergence of organ function, which in turn can impact developmental processes. Here we show that fluid flow-induced collective epithelial migration during kidney nephron morphogenesis induces cell stretch that in turn signals epithelial proliferation. Increased cell proliferation was dependent on PI3K signaling. Inhibiting epithelial proliferation by blocking PI3K or CDK4/Cyclin D1 activity arrested cell migration prematurely and caused a marked overstretching of the distal nephron tubule. Computational modeling of the involved cell processes predicted major morphological and kinetic outcomes observed experimentally under a variety of conditions. Overall, our findings suggest that kidney development is a recursive process where emerging organ function "feeds back" to the developmental program to influence fundamental cellular events such as cell migration and proliferation, thus defining final organ morphology.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0039992