Plzf regulates limb and axial skeletal patterning

The promyelocytic leukaemia zinc finger (Plzf) protein (encoded by the gene Zfp 145) belongs to the POZ/zinc-finger family of transcription factors. H ere we generate Zfp 145(-/-) mice and show that Plzf is essential for patte rning of the limb and axial skeleton. Plzf inactivation results in patterni ng defects affecting all skeletal structures of the limb, including homeoti c transformations of anterior skeletal elements into posterior structures. We demonstrate that Plzf acts as a growth-inhibitory and pro-apoptotic fact or in the limb bud. The expression of members of the abdominal b (Abdb) Hox gene complex, as well as genes encoding bone morphogenetic proteins (Bmps) . is altered in the developing limb of Zfp 145(-/-) mice. Plzf regulates th e expression of these genes in the absence of aberrant polarizing activity and independently of known patterning genes. Zfp145(-/-) mice also exhibit anterior-directed homeotic transformation throughout the axial skeleton wit h associated alterations in Hox gene expression. Plzf is therefore a mediat or of anterior-to-posterior (AP) patterning in both the axial and appendicu lar skeleton and acts as a regulator of Hox gene expression.