PAX7, a Key for Myogenesis Modulation in Muscular Dystrophies through Multiple Signaling Pathways: A Systematic Review  
[PERSON]  
1 Centre for Tissue Engineering & Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Cheras, Kuala Lumpur 56000, Malaysia; [EMAIL_ADDRESS] (N.L.A.R.)1 Centre for Tissue Engineering & Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Cheras, Kuala Lumpur 56000, Malaysia; idayuzham@ukam.  
prognosis of disease severity and lifespan expectancy [6; 7]. Muscular dystrophy can be characterized, although this varies, by the progression of muscle wasting and loss of muscle regeneration capabilities, leading to fragile fibers due to impaired myogenesis [8]. In the case of Duchenne Muscular Dystrophy, the catastrophic progression of muscle wasting leads to premature death [9].  
Myogenesis is a series of progressive development of skeletal muscle tissue over a lifetime where myoblasts, the early mononucleated committed precursor cells of skeletal muscle fuse together and differentiate into myotubes, the multinucleated muscle cells that later undergo further differentiation and fusion to form myofibers [10]. Myoblast heterogeneity stems from three types of myoblasts: embryonic, fetal, and satellite cells with distinct genetic backgrounds that are traditionally distinguished by desmin, myogenin (MyoG), and myosin heavy chain isoform (MyHC) expression [11; 12]. These myoblast transitions are thought to overlap at multiple points during myogenesis, due to the activation of several factors. Four myogenic regulatory factors (MRF), Myogenic factor 5 (Myf5), Mrf4, Myogenic Differentiation 1 (MyoD), and MyoG play critical roles in the precise differentiation of progenitor myoblasts into myofib during embryonic-to-adult myogenesis [13; 14].  
_Pax7_ is a transcription factor known to be indispensable in myogenesis by modulating _MyoD_ expression and maintaining healthy and mature cell differentiation [15; 16]. _Pax7_ belongs to the highly conserved paired-box (Pax) gene family transcription factor and is critically expressed during the development of the nervous and muscular systems [17]. Interestingly, it has been revealed that overexpression of _Pax7_ regulates myogenic differentiation by downregulating _MyoD_ expression and prevents _MyoG_ induction in fetal Duchenne Muscular Dystrophy (DMD) muscle tissues, suggesting a delay in myofib differentiation program [18; 19].  
Several major signaling pathways are intricately linked to each other in governing diseases, making it challenging to understand the orchestration of cellular events upon changes in gene expression. Therefore, in this review, we highlight the thorough evidence of Pax7's precise function in multiple signaling pathways. Moreover, this systematic review will provide insight into a decade of the relevant research evidence in Pax7 involvement in modulating myogenesis and deciding cell fate, with additional stress on the novel approach that could be taken in manipulating Pax7 expression itself in dystrophic muscle towards the discovery of effective treatment for muscular dystrophies.