title: Analysis of neural crest-derived clones reveals novel aspects of facial development.
abstract: Cranial neural crest cells populate the future facial region and produce ectomesenchyme-derived tissues, such as cartilage, bone, dermis, smooth muscle, adipocytes, and many others. However, the contribution of individual neural crest cells to certain facial locations and the general spatial clonal organization of the ectomesenchyme have not been determined. We investigated how neural crest cells give rise to clonally organized ectomesenchyme and how this early ectomesenchyme behaves during the developmental processes that shape the face. Using a combination of mouse and zebrafish models, we analyzed individual migration, cell crowd movement, oriented cell division, clonal spatial overlapping, and multilineage differentiation. The early face appears to be built from multiple spatially defined overlapping ectomesenchymal clones. During early face development, these clones remain oligopotent and generate various tissues in a given location. By combining clonal analysis, computer simulations, mouse mutants, and live imaging, we show that facial shaping results from an array of local cellular activities in the ectomesenchyme. These activities mostly involve oriented divisions and crowd movements of cells during morphogenetic events. Cellular behavior that can be recognized as individual cell migration is very limited and short-ranged and likely results from cellular mixing due to the proliferation activity of the tissue. These cellular mechanisms resemble the strategy behind limb bud morphogenesis, suggesting the possibility of common principles and deep homology between facial and limb outgrowth.
authors: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm SE-171 77, Sweden.
authors: Marketa
authors: M
authors: Kaucka
authors: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm SE-171 77, Sweden.; Research Center of Neurology, 125367 Moscow, Russia.
authors: Evgeny
authors: E
authors: Ivashkin
authors: Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm SE-171 77, Sweden.
authors: Daniel
authors: D
authors: Gyllborg
authors: Central European Institute of Technology, Brno University of Technology, 616 00 Brno, Czech Republic.
authors: Tomas
authors: T
authors: Zikmund
authors: Central European Institute of Technology, Brno University of Technology, 616 00 Brno, Czech Republic.
authors: Marketa
authors: 0000-0002-5200-7365
authors: M
authors: Tesarova
authors: Central European Institute of Technology, Brno University of Technology, 616 00 Brno, Czech Republic.
authors: Jozef
authors: 0000-0002-7397-125X
authors: J
authors: Kaiser
authors: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm SE-171 77, Sweden.
authors: Meng
authors: M
authors: Xie
authors: Department of Molecular Neurosciences, Medical University of Vienna, Vienna 1190, Austria.
authors: Julian
authors: J
authors: Petersen
authors: Division of Molecular Neurobiology, Medical Research Council National Institute for Medical Research, London NW7 1AA, UK.
authors: Vassilis
authors: V
authors: Pachnis
authors: Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milano, Italy.
authors: Silvia K
authors: 0000-0003-0378-3808
authors: SK
authors: Nicolis
authors: Department of Craniofacial Development and Stem Cell Biology, King's College London Dental Institute, Guy's Hospital, London SE1 9RT, UK.
authors: Tian
authors: T
authors: Yu
authors: Department of Craniofacial Development and Stem Cell Biology, King's College London Dental Institute, Guy's Hospital, London SE1 9RT, UK.
authors: Paul
authors: P
authors: Sharpe
authors: Unit of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm SE-171 77, Sweden.
authors: Ernest
authors: 0000-0003-0197-6577
authors: E
authors: Arenas
authors: Science for Life Laboratory, Royal Institute of Technology, Solna 17121, Sweden.
authors: Hjalmar
authors: 0000-0003-0578-4003
authors: H
authors: Brismar
authors: Science for Life Laboratory, Royal Institute of Technology, Solna 17121, Sweden.
authors: Hans
authors: 0000-0002-5584-9170
authors: H
authors: Blom
authors: Hubrecht Institute of the Royal Netherlands Academy of Arts and Sciences, Princess Maxima Centre and University Medical Centre Utrecht, 3584 Utrecht, Netherlands.
authors: Hans
authors: H
authors: Clevers
authors: Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich CH-8093, Switzerland.
authors: Ueli
authors: U
authors: Suter
authors: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm SE-171 77, Sweden.
authors: Andrei S
authors: AS
authors: Chagin
authors: Department of Neuroscience, Karolinska Institutet, Stockholm SE-171 77, Sweden.
authors: Kaj
authors: 0000-0002-9997-7078
authors: K
authors: Fried
authors: Department of Information Technology, Uppsala University, Uppsala SE-751 05, Sweden.
authors: Andreas
authors: A
authors: Hellander
authors: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm SE-171 77, Sweden.; Department of Molecular Neurosciences, Medical University of Vienna, Vienna 1190, Austria.
authors: Igor
authors: I
authors: Adameyko
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002999:Clone Cells / Q000166:cytology*; D004475:Ectoderm / Q000166:cytology / Q000196:embryology; D005145:Face / Q000196:embryology*; D015870:Gene Expression; D017930:Genes, Reporter; D021621:Imaging, Three-Dimensional; D008648:Mesoderm / Q000166:cytology / Q000196:embryology; D051379:Mice; D008953:Models, Anatomic; D009024:Morphogenesis; D009432:Neural Crest / Q000166:cytology*; D038081:Organogenesis; D010641:Phenotype; D015027:Zebrafish
keywords: Early face development; clonal envelopes; embryonic development; migration; morphogenesis; neural crest cells