title: Modeling digits. Digit patterning is controlled by a Bmp-Sox9-Wnt Turing network modulated by morphogen gradients.
abstract: During limb development, digits emerge from the undifferentiated mesenchymal tissue that constitutes the limb bud. It has been proposed that this process is controlled by a self-organizing Turing mechanism, whereby diffusible molecules interact to produce a periodic pattern of digital and interdigital fates. However, the identities of the molecules remain unknown. By combining experiments and modeling, we reveal evidence that a Turing network implemented by Bmp, Sox9, and Wnt drives digit specification. We develop a realistic two-dimensional simulation of digit patterning and show that this network, when modulated by morphogen gradients, recapitulates the expression patterns of Sox9 in the wild type and in perturbation experiments. Our systems biology approach reveals how a combination of growth, morphogen gradients, and a self-organizing Turing network can achieve robust and reproducible pattern formation.
authors.affiliation: Systems Biology Program, Centre for Genomic Regulation (CRG), and Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, 08003 Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Raspopovic
authors.affiliation: Systems Biology Program, Centre for Genomic Regulation (CRG), and Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, 08003 Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Marcon
authors.affiliation: Systems Biology Program, Centre for Genomic Regulation (CRG), and Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, 08003 Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Russo
authors.affiliation: Systems Biology Program, Centre for Genomic Regulation (CRG), and Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, 08003 Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys 23, 08010 Barcelona, Spain. james.sharpe@crg.eu.
authors.forename: J
authors.initials: J
authors.lastname: Sharpe
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D003198:Computer Simulation; D005121:Extremities / Q000196:embryology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018878:Limb Buds / Q000196:embryology*; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D055758:SOX9 Transcription Factor; D051153:Wnt Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins