The mouse polydactylous mutation, luxate (lx), causes anterior shift of the anteroposterior border in the developing hindlimb bud.
Pattern formation along the anterior-posterior axis of the vertebrate limb is established upon activation of Sonic Hedgehog (SHH) in the zone of polarizing activity (ZPA). Since many mouse mutants with preaxial polydactyly show ectopic expression of Shh at the anterior margin of the limb buds, it has been thought to be a primary defect caused by these mutations. We show here that the mouse mutation luxate (lx) exhibits dose-dependent reduction in the size of the Fgf8 expression domain in the ectoderm from the initial stage of limb development. This aberration was independent of Fgf10 expression in the limb mesenchyme. Shh was induced in the mesenchyme underlying the posterior end of the Fgf8 expression domain, indicating an anterior shift of Shh expression in lx hindlimb buds. Prior to the ectopic induction of Shh, the expression domains of genes downstream from Shh, namely dHAND, Gli1, Ptc and Gre, which are normally expressed in posterior mesenchyme of limb buds, expanded anteriorly on the lx hindlimb buds. Conversely, the expression domains of anterior mesenchymal markers such as Gli3and Alx4 decreased in size. Thus, ectopic Shh is not a primary defect of the lx mutation. Rather, our results indicate that the lx mutation affects the positioning of the anteroposterior border in developing hindlimb buds.
Yada
Yukari
Y
Ochanomizu University, Tokyo, Japan.
Makino
Shigeru
S
Chigusa-Ishiwa
Sadao
S
Shiroishi
Toshihiko
T
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D016923:Cell Death / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D004627:Embryonic Induction / Q000502:physiology; D051519:Fibroblast Growth Factor 4; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D018878:Limb Buds; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins; D017689:Polydactyly / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D029961:Zebrafish Proteins; D000074290:Zinc Finger Protein Gli3
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D051519:Fibroblast Growth Factor 4; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; D000074290:Zinc Finger Protein Gli3; C496446:Fgf4 protein, mouse; C496457:Fgf8 protein, mouse; C465571:Gli3 protein, mouse; C498766:Hand2 protein, mouse; C410915:hand2 protein, zebrafish