title: Inhibition of polarizing activity in the anterior limb bud is regulated by extracellular factors.
abstract: Anterior-posterior patterning of the developing limb is largely viewed as a function of polarizing activity. Recent evidence in polydactylous mutants, however, indicates that development of proper pattern also requires the involvement of inhibitory pathways in the anterior limb that prevent secondary polarizing zone formation, thus limiting the number of digits produced. We report the novel finding that grafts of extracellular matrix from the Mouse Posterior Limb Bud-4 cell line can induce supernumerary digits, including digits with posterior phenotype, from anterior chick limb mesenchyme. Unlike previously described mechanisms of pattern specification during limb development, it is shown that the extracellular matrix effect is not associated with release of an active signal. Rather, evidence is presented suggesting that heparan sulfate moieties in extracellular matrix grafts bind an endogenous, extracellular factor involved in inhibition of anterior polarizing activity, leading to derepression of the anterior limb and induction of polarizing zone marker genes including Sonic hedgehog and Bone morphogenetic protein-2.
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana 70118, USA. sschall@tulane.edu
authors.forename: S A
authors.initials: SA
authors.lastname: Schaller
authors.forename: K
authors.initials: K
authors.lastname: Muneoka
mesh_terms: D000818:Animals; D019521:Body Patterning; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D002642:Chick Embryo; D046508:Culture Techniques; D005109:Extracellular Matrix / Q000378:metabolism / Q000637:transplantation; D005121:Extremities / Q000196:embryology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D006025:Glycosaminoglycans / Q000378:metabolism; D053823:Hedgehog Proteins; D006497:Heparan Sulfate / Q000378:metabolism; D008648:Mesoderm / Q000637:transplantation; D051379:Mice; D017689:Polydactyly / Q000196:embryology / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D016212:Transforming Growth Factor beta; D014183:Transplantation, Heterologous
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016222:Fibroblast Growth Factor 2; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D006025:Glycosaminoglycans; D053823:Hedgehog Proteins; D006497:Heparan Sulfate; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; C525719:Bmp2 protein, mouse; C496457:Fgf8 protein, mouse