Disease relevance of PAX7

• Gain-of-function mutations creating fusion proteins consisting of PAX3 or PAX7 and another transcription factor of the forkhead family (FKHR) are associated with alveolar rhabdomyosarcomas [1].
• PAX7 expression in embryonal rhabdomyosarcoma suggests an origin in muscle satellite cells [2].
• FOXO1 gene is fused to PAX3 or PAX7 genes in rhabdomyosarcoma [3].
• Specifically, the gene ENO1 was amplified in six and the gene PAX7 in five out of 37 cases which included both biopsies and paraffin-embedded tissues of squamous cell lung carcinomas [4].
• Here we provide a novel perspective by correlating metastasis with expression of PAX3, PAX7 and ephrin/Eph receptors as well as NCAMs, cell surface markers normally involved in migration and adhesion during development, and propose a role for PAX genes in the increased metastatic potential of these tumours [5].

High impact information on PAX7

• PAX-1 and PAX-7 map to chromosomal regions containing previously assigned disease loci [6].
• We show that the microalga Phaeodactylum tricornutum can be genetically engineered to thrive on exogenous glucose in the absence of light through the introduction of a gene encoding a glucose transporter (glut1 or hup1) [7].
• The myogenic identity of precursor cells in the adult depends on Pax7, the orthologue of Pax3 which is required for early myogenesis; this finding is of major importance for muscle regeneration and the active field of stem cell research [8].
• Resident progenitor cells defined by Pax3/Pax7 expression are formed initially, but they are progressively lost and virtually absent at embryonic day 14 [9].
• Using physical mapping and cloning strategies, we determined that t(2;13) and t(1;13) rearrange PAX3 and PAX7, which encode members of the paired box transcription factor family, and juxtapose these genes with FKHR, which encodes a novel member of the fork head transcription factor family [10].

Biological context of PAX7

• In our study, we investigated alternative splicing of the wild-type and fusion forms of PAX3 and PAX7 in alveolar and embryonal RMS and assessed the functional implications [11].
• Our findings indicate that this t(1;13) rearranges PAX7 on chromosome 1 and fuses it to FKHR on chromosome 13 [12].
• Deletion analysis showed that the transactivation domains of PAX7 and PAX7-FKHR are each more potent than either full-length protein, and resistance to cis-repression is responsible for the PAX7-FKHR gain of function [13].
• Therefore, these translocations alter biological activity at the levels of protein function, gene expression, and subcellular localization with the cumulative outcome postulated to be aberrant regulation of PAX3/PAX7 target genes [14].
• In one case, amplification of the PAX7 gene and 3'-and 5'-FKHR gene sequences was demonstrated by using interphase fluorescence in situ hybridization on tumor imprints [15].

Anatomical context of PAX7

• This is corroborated by the detection of MET (c-met) expression, a marker for the myogenic satellite cell lineage, in all RMS samples expressing wild-type PAX7 [2].
• Mice with a mutated Pax7 gene suffer from defects in cephalic neural crest derivatives only and indicate that both genes may functionally share some redundancy [1].
• Pax3 and Pax7 are specifically expressed in the dorsal neural tube and the developing somite [1].
• Cells of embryonal RMS, the other major histiotype of this tumor, were found to express either wild type PAX3 or PAX7 at elevated levels when compared with primary human myoblasts [16].
• Transcription factors encoded by PAX3 and PAX7 are amongst the first expressed in the embryo, being principal regulators of neurogenic and myogenic progenitor cell specification and embryonic segmentation [5].

Associations of PAX7 with chemical compounds

• Several molecules have been implicated in the regulation of satellite cell quiescence, activation and renewal, including the transcription factors Pax7, MyoD and Myf5, the cell-surface glycoprotein CD34, and the membrane lipid sphingomyelin [17].

Other interactions of PAX7

• Finally, studies of ARMS tumors revealed CXCR4, PAX3, and PAX7 expression levels consistent with our cell culture results [18].
• No sequence variation was observed in the paired domain of the PAX7 and PAX9 genes [19].
• For PAX7 and PAX7-FKHR, there was a consistent pattern of co-expression of the 4 isoforms in RMS tumors: Q+GL- > Q+GL+ >/= Q-GL- > Q-GL+ [11].
• Two ARMS had the t(2;13)(q35;q14) and the third a PAX7/FKHR fusion, a cryptic t(1;13)(p36;q14), undetected by cytogenetic techniques, but revealed by reverse transcriptase polymerase chain reaction [20].
• It was discovered that the soleus contained a higher number of Pax7, MyoD, or myogenin-positive nuclei compared with the EDL [21].

Analytical, diagnostic and therapeutic context of PAX7

• Both alveolar and embryonal components of the mixed ARMS/ERMS subtype were negative for PAX3, PAX7, and FKHR rearrangements, a surprising finding confirmed by RT-PCR and/or conventional karyotyping [22].
• With the use of Southern blot methodology, rearrangements of the 30-kb PAX7 intron 7 were detected in 9 of 9 PAX7-FKHR-positive cases [23].
• Satellite cell proliferation was determined by PAX7 immunohistochemistry [24].
• On the other hand, transplantation of the mesencephalic floor plate into the dorsal mesencephalon suppressed PAX7 expression in the dorsal mesencephalon and changed its fate from the tectum to the tegmentum, indicating that factors in the mesencephalic floor plate suppress PAX7 and limit tectum territory to the dorsal part of the mesencephalon [25].
• Heterotopic transplantation of brain vesicles between chick and quail were performed, and the correlation between tectum formation and the expression of two PAX family genes, PAX7 and PAX6, analyzed [25].

References