TY - JOUR
T1 - The role of Alx-4 in the establishment of anteroposterior polarity during vertebrate limb development
AU - Takahashi, Motohisa
AU - Tamura, Koji
AU - Büscher, Dirk
AU - Masuya, Hiroshi
AU - Yonei-Tamura, Sayuri
AU - Matsumoto, Ken
AU - Naitoh-Matsuo, Mayumi
AU - Takeuchi, Jun
AU - Ogura, Keiko
AU - Shiroishi, Toshihiko
AU - Ogura, Toshihiko
AU - Belmonte, Juan Carlos Izpisúa
PY - 1998
Y1 - 1998
N2 - We have determined that Strong's Luxoid (lst(D)) mice have a 16 bp deletion in the homeobox region of the Alx-4 gene. This deletion, which leads to a frame shift and a truncation of the Alx-4 protein, could cause the polydactyly phenotype observed in 1st(D) mice. We have cloned the chick homologue of Alx-4 and investigated its expression during limb outgrowth. Chick Alx-4 displays an expression pattern complementary to that of shh, a mediator of polarizing activity in the limb bud. Local application of Sonic hedgehog (Shh) and Fibroblast Growth Factor (FGF), in addition to ectodermal apical ridge removal experiments suggest the existence of a negative feedback loop between Alx-4 and Shh during limb outgrowth. Analysis of polydactylous mutants indicate that the interaction between Alx-4 and Shh is independent of Gli3, a negative regulator of Shh in the limb. Our data suggest the existence of a negative feedback loop between Alx-4 and Shh during vertebrate limb outgrowth.
AB - We have determined that Strong's Luxoid (lst(D)) mice have a 16 bp deletion in the homeobox region of the Alx-4 gene. This deletion, which leads to a frame shift and a truncation of the Alx-4 protein, could cause the polydactyly phenotype observed in 1st(D) mice. We have cloned the chick homologue of Alx-4 and investigated its expression during limb outgrowth. Chick Alx-4 displays an expression pattern complementary to that of shh, a mediator of polarizing activity in the limb bud. Local application of Sonic hedgehog (Shh) and Fibroblast Growth Factor (FGF), in addition to ectodermal apical ridge removal experiments suggest the existence of a negative feedback loop between Alx-4 and Shh during limb outgrowth. Analysis of polydactylous mutants indicate that the interaction between Alx-4 and Shh is independent of Gli3, a negative regulator of Shh in the limb. Our data suggest the existence of a negative feedback loop between Alx-4 and Shh during vertebrate limb outgrowth.
KW - Alx-4
KW - Chick
KW - Limb development
KW - Mouse
KW - Polarizing activity
KW - shh
KW - Stong's Luxoid
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M3 - Article
C2 - 9778501
AN - SCOPUS:0031672928
SN - 0950-1991
VL - 125
SP - 4417
EP - 4425
JO - Development (Cambridge)
JF - Development (Cambridge)
IS - 22
ER -