The role of Alx-4 in the establishment of anteroposterior polarity during vertebrate limb development

Motohisa Takahashi; Koji Tamura; Dirk Büscher; Hiroshi Masuya; Sayuri Yonei-Tamura; Ken Matsumoto; Mayumi Naitoh-Matsuo; Jun Takeuchi; Keiko Ogura; Toshihiko Shiroishi; Toshihiko Ogura; Juan Carlos Izpisúa Belmonte

The role of Alx-4 in the establishment of anteroposterior polarity during vertebrate limb development

Motohisa Takahashi, Koji Tamura, Dirk Büscher, Hiroshi Masuya, Sayuri Yonei-Tamura, Ken Matsumoto, Mayumi Naitoh-Matsuo, Jun Takeuchi, Keiko Ogura, Toshihiko Shiroishi, Toshihiko Ogura^*, Juan Carlos Izpisúa Belmonte

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

94 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	4417-4425
Number of pages	9
Journal	Development
Volume	125
Issue number	22
State	Published - 1998
Externally published	Yes

Keywords

Alx-4
Chick
Limb development
Mouse
Polarizing activity
Stong's Luxoid
shh

ASJC Scopus subject areas

Molecular Biology
Developmental Biology

Cite this

@article{b4668febdc3649f4af0197d40581cc90,

title = "The role of Alx-4 in the establishment of anteroposterior polarity during vertebrate limb development",

abstract = "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.",

keywords = "Alx-4, Chick, Limb development, Mouse, Polarizing activity, Stong's Luxoid, shh",

author = "Motohisa Takahashi and Koji Tamura and Dirk B{\"u}scher and Hiroshi Masuya and Sayuri Yonei-Tamura and Ken Matsumoto and Mayumi Naitoh-Matsuo and Jun Takeuchi and Keiko Ogura and Toshihiko Shiroishi and Toshihiko Ogura and Belmonte, {Juan Carlos Izpis{\'u}a}",

year = "1998",

language = "English (US)",

volume = "125",

pages = "4417--4425",

journal = "Development",

issn = "0950-1991",

publisher = "Company of Biologists Ltd",

number = "22",

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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.

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KW - Chick

KW - Limb development

KW - Mouse

KW - Polarizing activity

KW - Stong's Luxoid

KW - shh

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M3 - Article

C2 - 9778501

AN - SCOPUS:0031672928

SN - 0950-1991

VL - 125

SP - 4417

EP - 4425

JO - Development

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ER -

The role of Alx-4 in the establishment of anteroposterior polarity during vertebrate limb development

Abstract

Keywords

ASJC Scopus subject areas

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