title: Modification of the zone of polarizing activity signal by trypsin.
abstract: Patterning of the developing vertebrate limb along the anterior-posterior axis is controlled by the zone of polarizing activity (ZPA) via the expression of Sonic hedgehog (Shh) and along the proximal-distal axis by the apical ectodermal ridge (AER) through the production of fibroblast growth factors (FGFs). ZPA grafting, as well as ectopic application of SHH to the anterior chick limb bud, demonstrate that digit patterning is largely influenced by these secreted factors. Although signal transduction pathways have been well characterized for SHH and for FGFs, little is known of how these signals are regulated extracellularly in the limb. The present study shows that alteration of the extracellular environment through trypsin treatment can have profound effects on digit patterning. These effects appear to be mediated by the induction of Shh in host tissues and by ectopic AER formation, implicating the extracellular matrix in regulating the signaling activities of key patterning genes in the limb.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Stefanov
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Ferrage
authors.forename: Nicholas F
authors.initials: NF
authors.lastname: Parchim
authors.forename: Christine E
authors.initials: CE
authors.lastname: Lee
authors.forename: Angela D
authors.initials: AD
authors.lastname: Reginelli
authors.forename: Mara
authors.initials: M
authors.lastname: Taché
authors.forename: Rosalie A
authors.initials: RA
authors.lastname: Anderson
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000187:drug effects* / Q000502:physiology; D002642:Chick Embryo / Q000002:abnormalities / Q000196:embryology*; D017364:Collagenases / Q000494:pharmacology; D004475:Ectoderm / Q000502:physiology / Q000637:transplantation; D004627:Embryonic Induction; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D005341:Fibrinolysin / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000502:physiology*; D018878:Limb Buds / Q000002:abnormalities / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism / Q000637:transplantation; D008297:Male; D051379:Mice; D009024:Morphogenesis / Q000187:drug effects; D010179:Pancreas / Q000196:embryology; D015398:Signal Transduction; D014183:Transplantation, Heterologous; D016042:Transplantation, Heterotopic; D014357:Trypsin / Q000494:pharmacology*; D014921:Wings, Animal / Q000002:abnormalities / Q000196:embryology
chemical_list: D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D005346:Fibroblast Growth Factors; D014357:Trypsin; D005341:Fibrinolysin; D017364:Collagenases