title: Knockdown of connexin43-mediated regulation of the zone of polarizing activity in the developing chick limb leads to digit truncation.
abstract: In the developing chick wing, the use of antisense oligodeoxynucleotides to transiently knock down the expression of the gap junction protein, connexin43 (Cx43), results in limb patterning defects, including deletion of the anterior digits. To understand more about how such defects arise, the effects of transient Cx43 knockdown on the expression patterns of several genes known to play pivotal roles in limb formation were examined. Sonic hedgehog (Shh), which is normally expressed in the zone of polarizing activity (ZPA) and is required to maintain both the ZPA and the apical ectodermal ridge (AER), was found to be downregulated in treated limbs within 30 h. Bone morphogenetic protein-2 (Bmp-2), a gene downstream of Shh, was similarly downregulated. Fibroblast growth factor-8 expression, however, was unaltered 30 h after treatment but was greatly reduced at 48 h post-treatment, when the AER begins to regress. Expressions of Bmp-4 and Muscle segment homeobox-like gene (Msx-1) were not affected at any of the time points examined. Cx43 expression is therefore involved in some, but not all patterning cascades, and appears to play a role in the regulation of ZPA activity.
authors.affiliation: Anatomy with Radiology, School of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Lee Yong
authors.initials: LY
authors.lastname: Law
authors.forename: Jun Sheng
authors.initials: JS
authors.lastname: Lin
authors.forename: David L
authors.initials: DL
authors.lastname: Becker
authors.forename: Colin R
authors.initials: CR
authors.lastname: Green
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology; D002642:Chick Embryo; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D016373:DNA, Antisense / Q000378:metabolism; D005121:Extremities / Q000196:embryology*; D018878:Limb Buds; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018031:Connexin 43; D016373:DNA, Antisense