A re-examination of proximodistal patterning during vertebrate limb development

• Published in: Nature (London) Vol. 418; no. 6897; pp. 539 - 544
• Main Authors: Tabin, Clifford J, Dudley, Andrew T, Ros, María A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01-08-2002; Nature Publishing Group
• Subjects: Anatomy & physiology; Animals; Arms; Biological and medical sciences; Body Patterning; Cell Death - drug effects; Cell Differentiation; Cell Division - drug effects; Cell Lineage; Chick Embryo; Ectoderm - cytology; Ectoderm - drug effects; Ectoderm - metabolism; Embryology: invertebrates and vertebrates. Teratology; Experimental organogenesis; Fibroblast Growth Factors - pharmacology; Fundamental and applied biological sciences. Psychology; Legs; Limb Buds - cytology; Limb Buds - drug effects; Limb Buds - embryology; Models, Biological; Organogenesis. Physiological fonctions; Vertebrates; Vertebrates - embryology; Wings, Animal - cytology; Wings, Animal - drug effects; Wings, Animal - embryology; Cell proliferation; Vertebrata; Ectoderm; Embryo; Distal; Limb; Development; Mesenchyma; Models; Chicken; Aves; Differentiation
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature00945

The 'progress zone' model provides a framework for understanding progressive development of the vertebrate limb. This model holds that undifferentiated cells in a zone of fixed size at the distal tip of the limb bud (the progress zone) undergo a progressive change in positional information such that their specification is altered from more proximal to more distal fates. This positional change is thought to be driven by an internal clock that is kept active as long as the cells remain in the progress zone. However, owing to cell division, the most proximal of these cells are continually pushed outside the confines of the zone. As they exit, clock function ceases and cells become fixed with the positional value last attained while within the zone. In contrast to this model, our data suggest that the various limb segments are 'specified' early in limb development as distinct domains, with subsequent development involving expansion of these progenitor populations before differentiation. We also find, however, that the distal limb mesenchyme becomes progressively 'determined', that is, irreversibly fixed, to a progressively limited range of potential proximodistal fates.