Expression of the zinc-finger gene PLZF at rhombomere boundaries in the vertebrate hindbrain.

Abstract

To investigate the potential biological role(s) of the PLZF gene, discovered as a fusion with the RARA locus in a patient with acute promyelocytic leukemia harboring a t(11;17) chromosomal translocation, we have isolated its murine homologue (mPLZF) and studied its patterns of developmental expression. The levels of mPLZF mRNAs increased perinatally in the liver, heart, and kidney, but with the exception of the heart, they were either absent or very low in the adult tissues. In situ analysis of mPLZF expression in mouse embryos between 7.0 and 10.5 days of development revealed that mPLZF mRNAs and proteins were coexpressed in spatially restricted and temporally dynamic patterns in the central nervous system. In the hindbrain region, a segmental pattern of expression correlated with the development of the rhombomeres. From 9.0 days of development, starting first in rhombomeres 3 and 5, there was an ordered down-regulation of expression in the center of each rhombomere, so that 1 day later elevated levels of mPLZF mRNAs and proteins were restricted to cells surrounding the rhombomeric boundaries. The chicken homologue of the PLZF gene, which we have also cloned, demonstrated a similar segmental pattern of expression in the hindbrain. To date, PLZF represents the only example of a transcription factor with elevated expression at rhombomeric boundaries. The high degree of evolutionary conservation between the patterns ofPLZF expression during mammalian and avian central nervous system development suggests that it has an important functional role in the regionalization of the vertebrate hindbrain, potentially regulating boundary cell interactions.

SMRT corepressor interacts with PLZF and with the PML-retinoic acid receptor α (RARα) and PLZF-RARα oncoproteins associated with acute promyelocytic leukemia

“…Unfortunately, the precise role of PLZF remains unclear. PLZF is a Krüppel-like nuclear protein which is likely involved in central nervous system development (13,14,25,37,39). Although no physiologically relevant DNA-binding sites or target genes have yet been reported for PLZF, many features of PLZF are shared with known transcription factors; it is therefore possible that PLZF is indeed a transcription factor and can regulate gene expression by tethering directly or indirectly (through an intermediary protein) to DNA.…”

Leukemia translocation protein PLZF inhibits cell growth and expression of cyclin A

“…PLZF is a sequence-speci®c DNA binding transcriptional repressor di erentially expressed during embryogenesis and in adult tissues (Avantaggiato et al, 1995;Cook et al, 1995). PLZF is expressed in human CD34 + cells and in multipotent progenitor cell lines such as FDCPMixA4 and at lower levels in more di erentiated myeloid cell lines (Reid et al, 1995).…”

PLZF induces megakaryocytic development, activates Tpo receptor expression and interacts with GATA1 protein

“…In murine embryos, PLZF is expressed in the aorta-gonad-mesonephros region Cook et al, 1995), where the hematopoietic stem cells were found to emerge from (Godin et al, 1993;Medvinsky et al, 1993). The molecular pathways through which PLZF exerts its function are still under investigation.…”