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Limb Patterning: From Signaling Gradients to Molecular Oscillations
Authors:Caroline J Sheeba  Raquel P Andrade  Isabel Palmeirim
Institution:1 Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal;2 ICVS/3B''s–PT Government Associate Laboratory, Braga/Guimarães, Portugal;3 Regenerative Medicine Program, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 8005-139 Faro, Portugal;4 IBB-Institute for Biotechnology and Bioengineering, Centro de Biomedicina Molecular e Estrutural, Universidade do Algarve, 8005-139 Faro, Portugal
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.
Keywords:RA  retinoic acid  FGF  fibroblast growth factor  SHH  sonic hedgehog  AER  apical ectodermal ridge  PD  proximal&ndash  distal  ZPA  zone of polarizing activity  AP  anterior&ndash  posterior
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