RNAi inhibition of Pax3/7 expression leads to markedly decreased expression of muscle determination genes. 2007

Satyakam Bhagavati, and Xiaosong Song, and M A Q Siddiqui
Department of Neurology, SUNY Downstate Medical Center, 450 Clarkson Ave, Brooklyn, NY 11203, USA. sbhagavati@downstate.edu

Skeletal muscle regeneration by cell transplantation for the treatment of muscle diseases requires the identification and isolation of well-defined, early skeletal muscle progenitor cells. It is known that myogenesis is governed by the sequential and compound activation of the muscle determination genes, the myogenic regulatory factors (MRFs). Recently it has been proposed that the transcription factors Pax3 and Pax7 trigger the expression of the MRFs and thereby specify a novel population of cells destined to enter the myogenic program. We directly tested this hypothesis using RNA interference methodology to reduce the levels of Pax3 and Pax7 RNA in mouse embryoid bodies developing in vitro. We found that decreasing the levels of Pax3/Pax7 RNA leads to a marked and selective decrease in Myf5, MyoD and Desmin expression. Pax3 and Pax7 expressing cells from developing embryos may thus serve as the earliest known skeletal muscle progenitor cells potentially useful for cell transplantation studies.

UI MeSH Term Description Entries
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D000072041 PAX3 Transcription Factor A paired box transcription factor that functions in CELL PROLIFERATION; CELL MIGRATION; and APOPTOSIS. It also is involved in MYOGENESIS and neural development. Mutations in the PAX3 gene are associated with WAARDENBURG SYNDROME TYPE 1. Paired Box 3 Protein,Paired Box Transcription Factor 3,Transcription Factor PAX3,Factor PAX3, Transcription,PAX3, Transcription Factor,Transcription Factor, PAX3
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D051761 Paired Box Transcription Factors A family of transcription factors that control EMBRYONIC DEVELOPMENT within a variety of cell lineages. They are characterized by a highly conserved paired DNA-binding domain that was first identified in DROSOPHILA segmentation genes. Paired Box Transcription Factor,Pax Transcription Factor,Pax Transcription Factors,Factor, Pax Transcription,Transcription Factor, Pax,Transcription Factors, Pax
D051763 PAX7 Transcription Factor A paired box transcription factor that is involved in EMBRYONIC DEVELOPMENT of the CENTRAL NERVOUS SYSTEM and SKELETAL MUSCLE. Paired Box Protein Pax-7,Paired Box Transcription Factor 7,Transcription Factor PAX7,Factor PAX7, Transcription,PAX7, Transcription Factor,Paired Box Protein Pax 7,Transcription Factor, PAX7
D053595 Embryonic Stem Cells Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells. Stem Cells, Embryonic,Cell, Embryonic Stem,Cells, Embryonic Stem,Embryonic Stem Cell,Stem Cell, Embryonic
D018006 Myogenic Regulatory Factors A family of muscle-specific transcription factors which bind to DNA in control regions and thus regulate myogenesis. All members of this family contain a conserved helix-loop-helix motif which is homologous to the myc family proteins. These factors are only found in skeletal muscle. Members include the myoD protein (MYOD PROTEIN); MYOGENIN; myf-5, and myf-6 (also called MRF4 or herculin). Myogenic Regulatory Factor,Factor, Myogenic Regulatory,Factors, Myogenic Regulatory,Regulatory Factor, Myogenic,Regulatory Factors, Myogenic
D018507 Gene Expression Regulation, Developmental Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism. Developmental Gene Expression Regulation,Embryologic Gene Expression Regulation,Gene Expression Regulation, Embryologic,Regulation of Gene Expression, Developmental,Regulation of Gene Expression, Embryologic,Regulation, Gene Expression, Developmental,Regulation, Gene Expression, Embryologic
D034622 RNA Interference A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process. Gene Silencing, Post-Transcriptional,Post-Transcriptional Gene Silencing,Co-Suppression,Cosuppression,Posttranscriptional Gene Silencing,RNA Silencing,RNAi,Co Suppression,Gene Silencing, Post Transcriptional,Gene Silencing, Posttranscriptional,Gene Silencings, Posttranscriptional,Interference, RNA,Post Transcriptional Gene Silencing,Post-Transcriptional Gene Silencings,Silencing, Post-Transcriptional Gene

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