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Knockdown of connexin43‐mediated regulation of the zone of polarizing activity in the developing chick limb leads to digit truncation
Author(s) -
Law Lee Yong,
Lin Jun Sheng,
Becker David L.,
Green Colin R.
Publication year - 2002
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1046/j.1440-169x.2002.00666.x
Subject(s) - zone of polarizing activity , gene knockdown , apical ectodermal ridge , limb development , sonic hedgehog , microbiology and biotechnology , limb bud , bone morphogenetic protein , fibroblast growth factor , noggin , hedgehog , homeobox , biology , anatomy , gene expression , ectoderm , chemistry , gene , signal transduction , genetics , receptor , embryogenesis , embryo
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.