Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 426, Issue 4, Pages 780-784Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2013.11.022
Keywords
fibroblast growth factors; sonic hedgehog; retinoic acid; molecular clock; limb pattern formation
Categories
Funding
- Fundacao para a Ciencia e a Tecnologia, Portugal [SFRH/BPD/89493/2012]
- Portuguese Government
- Programa Operacional Regional do Norte (ON.2) [NORTE-07-0124-FEDER-000017]
- Institute for Biotechnology and Bioengineering/Centro de Biomedicina Molecular e Estrutural, LA
- Fundacao para a Ciencia e a Tecnologia [PTDC/SAU-OBD/099758/2008, PTDC/SAU-BID/121459/2010]
- [PEst-OE/EQB/LA0023/2011]
- Fundação para a Ciência e a Tecnologia [PEst-OE/EQB/LA0023/2011, PTDC/SAU-OBD/099758/2008, PTDC/SAU-BID/121459/2010] Funding Source: FCT
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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. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
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