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Publication : Interactions between HOXD and Gli3 genes control the limb apical ectodermal ridge via Fgf10.

First Author  Zakany J Year  2007
Journal  Dev Biol Volume  306
Issue  2 Pages  883-93
PubMed ID  17467687 Mgi Jnum  J:122561
Mgi Id  MGI:3714680 Doi  10.1016/j.ydbio.2007.03.517
Citation  Zakany J, et al. (2007) Interactions between HOXD and Gli3 genes control the limb apical ectodermal ridge via Fgf10. Dev Biol 306(2):883-93
abstractText  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.
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