Disease relevance of Pax7

• Infection of CD45(+):Sca1(+) cells from uninjured muscle with retrovirus expressing Pax7 efficiently activated the myogenic program [1].
• Pax3:Fkhr interferes with embryonic Pax3 and Pax7 function: implications for alveolar rhabdomyosarcoma cell of origin [2].
• Moreover, Fos is able to repress Pax7 expression in rhabdomyosarcoma cell lines and primary myoblasts, suggesting a molecular link to genetic alterations involved in human rhabdomyosarcomas [3].

High impact information on Pax7

• Cell culture and electron microscopic analysis revealed a complete absence of satellite cells in Pax7(-/-) skeletal muscle [4].
• Importantly, stem cells from Pax7(-/-) muscle displayed almost a 10-fold increase in their ability to form hematopoietic colonies [4].
• The paired box transcription factor Pax7 was isolated by representational difference analysis as a gene specifically expressed in cultured satellite cell-derived myoblasts [4].
• Pax7 is required for the specification of myogenic satellite cells [4].
• Pax3/Pax7 mark a novel population of primitive myogenic cells during development [5].

Biological context of Pax7

• In neural tube and somite regions where cell survival is maintained, the closely related Pax7 gene is upregulated, and its expression becomes expanded into the dorsal neural tube and somites, where Pax3 would normally be expressed [6].
• These results establish that Pax3 has complementary functions in MyoD activation and inhibition of apoptosis in the somitic mesoderm and in repression of Pax7 during neural tube and somite development [6].
• Finally, the retinal phenotype observed in Pax7-/- knock-out mice suggests a role for Pax7 in photoreceptor cell differentiation, retinal lamination and in the etiopathology of retinoblastoma [7].
• Comparative expression analysis of Pax3 and Pax7 during mouse myogenesis [8].
• In contrast, activation later in embryogenesis in cells that express Pax7 results in viable animals with a postnatal growth defect and a moderately decreased Pax7+ muscle satellite cell pool, phenocopying Pax7 deficiency but remarkably not leading to tumors [2].

Anatomical context of Pax7

• The growth and repair of skeletal muscle after birth depends on satellite cells that are characterized by the expression of Pax7 [9].
• Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cells [9].
• Pax3 and Pax7 are expressed in commissural neurons and restrict ventral neuronal identity in the spinal cord [10].
• Whilst initial Pax7-specification of the mesencephalon is well-established, a role in regulating polarity within the maturing mouse superior colliculus is yet to be defined, although already detailed for the chick tectum [11].
• These results implicate Pax7 as an important determinant of polarity within the mouse superior colliculus, and suggest a role in retinotopic mapping [11].

Associations of Pax7 with chemical compounds

• We have identified alternatively spliced isoforms of murine Pax-3 and Pax-7 which differ by the presence or absence of a single glutamine residue in a linker region which separates two distinct DNA-binding subdomains within the paired domain [12].

Regulatory relationships of Pax7

• Taken together, these results indicate that Pax7 is necessary and sufficient to induce the myogenic specification of CD45(+) stem cells resident in adult skeletal muscle [1].
• Co-culture with myoblasts or forced expression of MyoD also induced muscle differentiation of muscle SP cells prepared from mice lacking Pax7 gene, an essential gene for satellite cell development [13].

Other interactions of Pax7

• Manipulation of the dominant-negative forms of these factors in satellite cell cultures demonstrates that Pax3 cannot replace the antiapoptotic function of Pax7 [9].
• 5. In contrast, Pax7 expression is shared among all striated muscles and exhibits a uniform pattern [8].
• Analysis of the opb mutant phenotype and of opb/opb <--> wild-type chimeric embryos reveals that early in neural development, the wild-type opb gene (opb(+)) is required cell autonomously for the expression of Pax7 in dorsal cells and Pax6 in lateral cells [14].
• Pax-1 and the human gene HuP48 have identical paired domains, as do Pax-3 and HuP2 as well as Pax-7 and HuP1, and are likely to represent homologous genes in mouse and man [15].
• Sublaminal cells expressed unambiguous satellite cell markers (M-cadherin, Pax7, NCAM) and fused into scattered GFP+ muscle fibers [16].

Analytical, diagnostic and therapeutic context of Pax7

• In situ hybridization revealed that Pax7 was also expressed in satellite cells residing in adult muscle [4].
• To investigate the mechanism of these contrasting phenotypes, we replaced Pax3 by Pax7 by using gene targeting in the mouse [17].
• The expression profiles of Pax7 alternate transcripts were then assessed by RNA isolation and RT-PCR [18].
• Southern blotting indicated that SJL/J, Quackenbush and DDO mice share a Pax7/TaqI RFLP which differs from all other laboratory strains tested [19].
• Total RNA was isolated from adult mouse tissues and the polymerase chain reaction was performed on reverse transcribed mRNA using primers specific for regions that encode the paired and homeodomain of Pax7 [20].

References