Abstract
Skeletal muscle is a heterogeneous tissue that represents between 30 and 38% of the human body mass and has important functions in the organism, such as maintaining posture, locomotor impulse, or pulmonary ventilation. The genesis of skeletal muscle during embryonic development is a process controlled by an elaborate regulatory network combining the interplay of extrinsic and intrinsic regulatory mechanisms that transform myogenic precursor cells into functional muscle fibers through a finely tuned differentiation program. However, the capacity of generating muscle still remains once these fibers have matured. Adult myogenesis resembles many of the embryonic morphogenetic episodes and depends on the activation of satellite cells that have the potential to differentiate into new muscle fibers. Pitx2 is a member of the bicoid family of homeodomain transcription factors that play an important role in morphogenesis. In the last decade, Pitx2 has emerged as a key element involved in the fine-tuning mechanism that regulates skeletal-muscle development as well as the differentiation and cell fate of satellite cells in adult muscle. Here we present an integrative view of all aspects of embryonic and adult myogenesis in which Pitx2 is involved, from embryonic development to satellite-cell proliferation, fate specification, and differentiation. Those new Pitx2 functions on satellite-cell biology might open new perspectives to develop therapeutic strategies for muscular disorders.
Highlights
Skeletal muscle is a heterogeneous tissue that represents between 30 and 38% of the human body mass (Janssen et al, 2000)
The intrinsic elements form hierarchical interactions between transcriptional regulators, regulatory RNAs, and chromatin-remodeling factors. In this sense, during embryogenesis, muscle progenitors are specified by the sequential expression of a network of transcription factors composed of PAX3 and PAX7, and the basic helix-loop-helix myogenic regulatory factors (MRFs) MYOD, Pitx2 and Myogenesis
We have previously demonstrated that Pitx2c is the main Pitx2isoform expressed in Sol8 myoblasts and that overexpression of Pitx2c in Sol8 cells led to an increase in proliferative capacity and completely blocked terminal differentiation, mainly because high levels of Pax3 expression were maintained (Martínez-Fernández et al, 2006)
Summary
Skeletal muscle is a heterogeneous tissue that represents between 30 and 38% of the human body mass (Janssen et al, 2000). During adult life the skeletal muscle has the ability to resume developmental mechanisms that compensate for the physiological turnover and damage in order to maintain tissue homeostasis (Schmalbruch and Lewis, 2000; Pellettieri and Alvarado, 2007). This adult myogenesis depends on the activation of satellite cells (SCs), that have the potential to proliferate, differentiate, and generate new fibers, or repair existing ones (Chargé and Rudnicki, 2004). We discuss the potential therapeutic use of Pitx in the future
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