Cux2 refines the forelimb field by controlling expression of and genes.

In vertebrates, two pairs of buds that give rise to the fore- and hindlimbs form at discrete positions along the rostral-caudal axis of the body. The mechanism responsible for the positioning of the limb buds is still largely unknown. Here we show a novel function for Cut homeobox transcription factor 2 (Cux2), the ortholog of cut, in refining the forelimb field during chick development. is expressed in the forelimb field before the emergence of the limb buds. Knocking down the expression of using small interfering RNA (siRNA) resulted in a caudal shift of the forelimb bud, whereas misexpression of or the constitutively active - caused a rostral shift of the forelimb bud or reduction of the forelimb field along the anterior-posterior axis. Further functional analyses revealed that expression of genes and (), which are involved in limb positioning, are directly activated by Cux2 in the lateral plate mesoderm. Our data suggest that Cux2 in the lateral plate mesoderm refines the forelimb field via regulation of and genes in chicken embryos.