title: Reconciling diverse mammalian pigmentation patterns with a fundamental mathematical model.
abstract: Bands of colour extending laterally from the dorsal to ventral trunk are a common feature of mouse chimeras. These stripes were originally taken as evidence of the directed dorsoventral migration of melanoblasts (the embryonic precursors of melanocytes) as they colonize the developing skin. Depigmented 'belly spots' in mice with mutations in the receptor tyrosine kinase Kit are thought to represent a failure of this colonization, either due to impaired migration or proliferation. Tracing of single melanoblast clones, however, has revealed a diffuse distribution with high levels of axial mixing--hard to reconcile with directed migration. Here we construct an agent-based stochastic model calibrated by experimental measurements to investigate the formation of diffuse clones, chimeric stripes and belly spots. Our observations indicate that melanoblast colonization likely proceeds through a process of undirected migration, proliferation and tissue expansion, and that reduced proliferation is the cause of the belly spots in Kit mutants.
authors.affiliation: MRC Human Genetics Unit, MRC IGMM, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Mort
authors.affiliation: Wolfson Centre for Mathematical Biology, University of Oxford, Andrew Wiles Building, Woodstock Road, Oxford OX2 6GG, UK.
authors.forename: Robert J H
authors.initials: RJH
authors.lastname: Ross
authors.affiliation: MRC Human Genetics Unit, MRC IGMM, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK.
authors.forename: Kirsten J
authors.initials: KJ
authors.lastname: Hainey
authors.affiliation: MRC Human Genetics Unit, MRC IGMM, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK.
authors.forename: Olivia J
authors.initials: OJ
authors.lastname: Harrison
authors.affiliation: MRC Human Genetics Unit, MRC IGMM, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Keighren
authors.affiliation: Oral Pathology Unit, School of Dentistry, College of Medical and Dental Sciences, University of Birmingham, St Chad's, Queensway, Birmingham B4 6NN, UK.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Landini
authors.affiliation: Wolfson Centre for Mathematical Biology, University of Oxford, Andrew Wiles Building, Woodstock Road, Oxford OX2 6GG, UK.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Baker
authors.affiliation: Department of Mathematics and Maxwell Institute for Mathematical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Painter
authors.affiliation: MRC Human Genetics Unit, MRC IGMM, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK.|Roslin Institute, University of Edinburgh, Roslin EH25 9RG, UK.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Jackson
authors.affiliation: Centre for Mathematical Biology, Department of Mathematical Sciences, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Yates
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D010860:Pigments, Biological / Q000502:physiology*; D012867:Skin / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D010860:Pigments, Biological