title: Mechanical stretch and PI3K signaling link cell migration and proliferation to coordinate epithelial tubule morphogenesis in the zebrafish pronephros.
abstract: 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.
authors: Department of Pathology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America. avasilyev@partners.org
authors: Aleksandr
authors: A
authors: Vasilyev
authors: Yan
authors: Y
authors: Liu
authors: Nathan
authors: N
authors: Hellman
authors: Narendra
authors: N
authors: Pathak
authors: Iain A
authors: IA
authors: Drummond
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002465:Cell Movement; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology*; D007684:Kidney Tubules / Q000166:cytology* / Q000196:embryology; D055595:Mechanical Phenomena; D008954:Models, Biological; D009024:Morphogenesis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D060910:Pronephros / Q000166:cytology / Q000196:embryology*; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology*
chemical_list: D019869:Phosphatidylinositol 3-Kinases