title: Limb patterning: from signaling gradients to molecular oscillations.
abstract: The developing forelimb is patterned along the proximal-distal and anterior-posterior axes by opposing gradients of retinoic acid and fibroblast growth factors and by graded sonic hedgehog signaling, respectively. However, how coordinated patterning along both axes is accomplished with temporal precision remains unknown. The limb molecular oscillator hairy2 was recently shown to be a direct readout of the combined signaling activities of retinoic acid, fibroblast growth factor and sonic hedgehog in the limb mesenchyme. Herein, an integrated time-space model is presented to conciliate the progress zone and two-signal models for limb patterning. We propose that the limb clock may allow temporal information to be decoded into positional information when the distance between opposing signaling gradients is no longer sufficient to provide distinct cell fate specification.
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal; Regenerative Medicine Program, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 8005-139 Faro, Portugal; IBB-Institute for Biotechnology and Bioengineering, Centro de Biomedicina Molecular e Estrutural, Universidade do Algarve, 8005-139 Faro, Portugal.
authors: Caroline J
authors: CJ
authors: Sheeba
authors: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors: Raquel P
authors: RP
authors: Andrade
authors: Regenerative Medicine Program, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 8005-139 Faro, Portugal; IBB-Institute for Biotechnology and Bioengineering, Centro de Biomedicina Molecular e Estrutural, Universidade do Algarve, 8005-139 Faro, Portugal. Electronic address: imesteves@ualg.pt.
authors: Isabel
authors: I
authors: Palmeirim
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002642:Chick Embryo; D005121:Extremities / Q000196:embryology*; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000072056:Transcription Factor HES-1; D014212:Tretinoin / Q000378:metabolism; D000074290:Zinc Finger Protein Gli3
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019485:Bone Morphogenetic Proteins; D005346:Fibroblast Growth Factors; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D000072056:Transcription Factor HES-1; D014212:Tretinoin; D000074290:Zinc Finger Protein Gli3; C465571:Gli3 protein, mouse; C489734:Hes1 protein, mouse; C465570:Shh protein, mouse
keywords: AER; AP; FGF; PD; RA; SHH; ZPA; anterior–posterior; apical ectodermal ridge; fibroblast growth factor; fibroblast growth factors; limb pattern formation; molecular clock; proximal–distal; retinoic acid; sonic hedgehog; zone of polarizing activity