title: Distribution of polarizing activity and potential for limb formation in mouse and chick embryos and possible relationships to polydactyly.
abstract: A central feature of the tetrapod body plan is that two pairs of limbs develop at specific positions along the head-to-tail axis. However, the potential to form limbs in chick embryos is more widespread. This could have implications for understanding the basis of limb abnormalities. Here we extend the analysis to mouse embryos and examine systematically the potential of tissues in different regions outside the limbs to contribute to limb structures. We show that the ability of ectoderm to form an apical ridge in response to FGF4 in both mouse and chick embryos exists throughout the flank as does ability of mesenchyme to provide a polarizing region signal. In addition, neck tissue has weak polarizing activity. We show, in chick embryos, that polarizing activity of tissues correlates with the ability either to express Shh or to induce Shh expression. We also show that cells from chick tail can give rise to limb structures. Taken together these observations suggest that naturally occurring polydactyly could involve recruitment of cells from regions adjacent to the limb buds. We show that cells from neck, flank and tail can migrate into limb buds in response to FGF4, which mimics extension of the apical ectodermal ridge. Furthermore, when we apply simultaneously a polarizing signal and a limb induction signal to early chick flank, this leads to limb duplications.
authors.affiliation: Department of Anatomy and Physiology, Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee DD1 5EH, UK. m.tanaka@dundee.ac.uk.
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: M J
authors.initials: MJ
authors.lastname: Cohn
authors.forename: P
authors.initials: P
authors.lastname: Ashby
authors.forename: M
authors.initials: M
authors.lastname: Davey
authors.forename: P
authors.initials: P
authors.lastname: Martin
authors.forename: C
authors.initials: C
authors.lastname: Tickle
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002642:Chick Embryo; D004475:Ectoderm / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D005121:Extremities / Q000196:embryology* / Q000473:pathology; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018878:Limb Buds / Q000378:metabolism / Q000637:transplantation; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D009333:Neck / Q000196:embryology; D017689:Polydactyly / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000494:pharmacology; D013623:Tail / Q000196:embryology; D015534:Trans-Activators; D014921:Wings, Animal / Q000196:embryology
chemical_list: C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D053823:Hedgehog Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D005346:Fibroblast Growth Factors