Ret and Etv4 Promote Directed Movements of Progenitor Cells during Renal Branching Morphogenesis

• DOI: 10.1371/journal.pbio.1002382
• Publication Date: 2016-02-19T18:34:16Z
• Authors: Paul Riccio; Cristina Cebrian; Hui Zong; Simon Hippenmeyer; Frank Costantini
• Keywords: Ureteric bud; Mesenchyme; Proto-Oncogene Proteins c-ret; Cell type

Branching morphogenesis of the epithelial ureteric bud forms renal collecting duct system and is critical for normal nephron number, while low number implicated in hypertension disease. Ureteric growth branching requires GDNF signaling from surrounding mesenchyme to cells at tips, via Ret receptor tyrosine kinase coreceptor Gfrα1; up-regulates transcription factors Etv4 Etv5, which are also branching. Despite extensive knowledge genetic control these events, it not understood, cellular level, how achieved or influences cell behaviors promote this process. Analysis chimeric embryos previously suggested a role promoting rearrangements nephric duct, but method was unsuited study individual during Here, we use Mosaic with Double Markers (MADM), combined organ culture time-lapse imaging, trace movements divisions tip cells. We first examine wild-type clones then mutant/wild-type mutant sister differentially heritably marked by green red fluorescent proteins. find that, kidneys, most behave as self-renewing progenitors, some whose progeny remain tips others populate growing UB trunks. In MADM clones, generated much more likely at, move to, new elongation, their Ret−/− Etv4−/− tend lag behind contribute only By tracking successive mitoses lineage, that has little effect on proliferation, contrast its effects movement. Our results show Ret/Etv4 promotes directed suggest model mediate morphogenesis.