Interactions between HOXD and Gli3 genes control the limb apical ectodermal ridge via Fgf10.
The development of the vertebrate limb is dependent upon two signaling centers, the apical ectodermal ridge (AER), which provides the underlying mesenchyme with essential growth factors, and the zone of polarizing activity (ZPA), the source of the Sonic hedgehog (SHH) product. Recent work involving gain and loss of function of Hox genes has emphasized their impact both on AER maintenance and Shh transcriptional activation. Here, we describe antagonistic interactions between posterior Hoxd genes and Gli3, suggesting that the latter product protects the AER from the deleterious effect of the formers, and we present evidence that Fgf10 is the mediator of HOX-dependent AER expansion. Furthermore, the striking similarity between some of the hereby observed Hox/Gli3-dependent morphogenetic defects and those displayed by fetuses with severely altered retinoic acid metabolism suggests a tight connection between these various pathways. The nature of these potential interactions is discussed in the context of proximal-distal growth and patterning.
Zakany
Jozsef
J
Department of Zoology and Animal Biology and National Research Centre/Frontiers in Genetics, University of Geneva, Sciences III, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
Zacchetti
Giovanna
G
Duboule
Denis
D
D000818:Animals; D019521:Body Patterning; D004475:Ectoderm / Q000378:metabolism*; D005121:Extremities / Q000196:embryology*; D051526:Fibroblast Growth Factor 10 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006720:Homozygote; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology*; D018878:Limb Buds / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D015398:Signal Transduction; D015533:Transcriptional Activation; D000074290:Zinc Finger Protein Gli3
C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; C465571:Gli3 protein, mouse; D018398:Homeodomain Proteins; C486697:Hoxd1 protein, mouse; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D000074290:Zinc Finger Protein Gli3