Plzf regulates limb and axial skeletal patterning

Abstract

The promyelocytic leukaemia zinc finger (Plzf) protein (encoded by the gene Zfp145) belongs to the POZ/zinc-finger family of transcription factors. Here we generate Zfp145-/- mice and show that Plzf is essential for patterning of the limb and axial skeleton. Plzf inactivation results in patterning defects affecting all skeletal structures of the limb, including homeotic transformations of anterior skeletal elements into posterior structures. We demonstrate that Plzf acts as a growth-inhibitory and pro-apoptotic factor 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 Zfp145-/- mice. Plzf regulates the 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 with associated alterations in Hox gene expression. Plzf is therefore a mediator of anterior-to-posterior (AP) patterning in both the axial and appendicular skeleton and acts as a regulator of Hox gene expression.

Human endogenous retrovirus protein cORF supports cell transformation and associates with the promyelocytic leukemia zinc finger protein

“…Remarkably, PLZFde®cient mice show no apparent disturbance in hematopoiesis but rather exhibit severe testicular dysfunction, among other defects (Barna et al, 2000;Hawe et al, 1996). Furthermore, cyclin A has recently been identi®ed as one PLZF target gene, and cyclin A subtypes are considered to possess regulatory functions in murine spermatogenesis (Ravnik and Wolgemuth, 1999).…”

“…Remarkably, PLZF is expressed in several human tissues, among them the testis (Zhang et al, 1999). Of note, PLZF null mice neither display any apparent disturbance of hematopoiesis nor develop leukemia but instead show defects in limb and axial skeletal patterning (Barna et al, 2000) and in spermatogenesis and testis development (Hawe et al, 1996). We report here that cORF, a protein encoded by human endogenous retroviruses transcribed in germ cell tumors, interacts with the PLZF transcriptional repressor.…”

Gdnf signaling pathways within the mammalian spermatogonial stem cell niche

“…It is a transcriptional repressor that inhibits stem cell differentiation and helps maintaining their presence in the niche. Plzf was originally identified in hematopoietic stem cells, but is also crucial for the patterning of the axial skeleton and the limbs (Reid et al, 1995;Barna et al, 2000). Plzf expression is high in undifferentiated multipotential hematopoietic progenitor cells, and low in differentiated cells (Reid et al, 1995).…”

The alpha subunit of Go interacts with promyelocytic leukemia zinc finger protein and modulates its functions

“…Several reports show that PLZF induces growth suppression, apoptosis, and cell cycle arrest [7,8,23]. Analysis of PLZF knock-out mice revealed that the protein is a growth inhibitory and proapoptotic factor in the limb bud in vivo [35]. Interestingly, treatment with cannabinoids or overexpression of PLZF inhibits growth of prostate cancer cells [36][37][38].…”