title: A self-avoidance mechanism in patterning of the urinary collecting duct tree.
abstract: BACKGROUND
  Glandular organs require the development of a correctly patterned epithelial tree. These arise by iterative branching: early branches have a stereotyped anatomy, while subsequent branching is more flexible, branches spacing out to avoid entanglement. Previous studies have suggested different genetic programs are responsible for these two classes of branches.
  
  
  RESULTS
  Here, working with the urinary collecting duct tree of mouse kidneys, we show that the transition from the initial, stereotyped, wide branching to narrower later branching is independent from previous branching events but depends instead on the proximity of other branch tips. A simple computer model suggests that a repelling molecule secreted by branches can in principle generate a well-spaced tree that switches automatically from wide initial branch angles to narrower subsequent ones, and that co-cultured trees would distort their normal shapes rather than colliding. We confirm this collision-avoidance experimentally using organ cultures, and identify BMP7 as the repelling molecule.
  
  
  CONCLUSIONS
  We propose that self-avoidance, an intrinsically error-correcting mechanism, may be an important patterning mechanism in collecting duct branching, operating along with already-known mesenchyme-derived paracrine factors.
authors.affiliation: University of Edinburgh, Edinburgh, EH8 9XB, UK. jamie.davies@ed.ac.uk.
authors.forename: Jamie A
authors.initials: JA
authors.lastname: Davies
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, EH25 9RG, UK. Peter.Hohenstein@roslin.ed.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: Hohenstein
authors.affiliation: University of Edinburgh, Edinburgh, EH8 9XB, UK. C.Chang-19@sms.ed.ac.uk.
authors.forename: C-Hong
authors.initials: CH
authors.lastname: Chang
authors.affiliation: The Institute of Genetics and Molecular Medicine, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK. rachel.berry@igmm.ed.ac.uk.
authors.forename: Rachel
authors.initials: R
authors.lastname: Berry
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D019521:Body Patterning; D055419:Bone Morphogenetic Protein 7 / Q000502:physiology; D003198:Computer Simulation; D007668:Kidney / Q000033:anatomy & histology / Q000196:embryology*; D008822:Mice, Transgenic; D008954:Models, Biological; D020794:Receptor Protein-Tyrosine Kinases; D015398:Signal Transduction; D046509:Tissue Culture Techniques; D014513:Ureter / Q000196:embryology*
chemical_list: D055419:Bone Morphogenetic Protein 7; C525820:bmp7 protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases