Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cells

Abstract

The growth and repair of skeletal muscle after birth depends on satellite cells that are characterized by the expression of Pax7. We show that Pax3, the paralogue of Pax7, is also present in both quiescent and activated satellite cells in many skeletal muscles. Dominant-negative forms of both Pax3 and -7 repress MyoD, but do not interfere with the expression of the other myogenic determination factor, Myf5, which, together with Pax3/7, regulates the myogenic differentiation of these cells. In Pax7 mutants, satellite cells are progressively lost in both Pax3-expressing and -nonexpressing muscles. We show that this is caused by satellite cell death, with effects on the cell cycle. Manipulation of the dominant-negative forms of these factors in satellite cell cultures demonstrates that Pax3 cannot replace the antiapoptotic function of Pax7. These findings underline the importance of cell survival in controlling the stem cell populations of adult tissues and demonstrate a role for upstream factors in this context.

Pericytes resident in postnatal skeletal muscle differentiate into muscle fibres and generate satellite cells

“…We found the highest number of β-gal + fibres and β-gal + satellite cells in muscles where Pax3 is expressed postnatally, such as forelimb muscles and Diaphragm 43 . Furthermore, we observed that these AP + vessel-associated cells express Pax3 in young animals (D.A., C.D.…”

MicroRNA-431 accelerates muscle regeneration and ameliorates muscular dystrophy by targeting Pax7 in mice

“…A dult skeletal muscle has a remarkable regenerative capacity that is attributable to satellite cells (SCs), which express the paired-box transcriptional factor Pax7 (refs [1][2][3][4]. In resting muscle, SCs are mostly quiescent; however, in response to stress or injury, they become activated and proliferated and either undergo differentiation or self-renewal to replenish the quiescent cell pool [5][6][7][8] .…”

“…In Pax7 knockout mice, the SC lineage is progressively lost through defective proliferation and self-renewal and precocious differentiation 1,4,10,15 . Pax7 also helps to direct and maintain the lineage specification of SCs, which in the absence of Pax7 and Pax3 differentiate into cartilage and other nonmuscle cell types 16 .…”

Bone Marrow-Derived Hematopoietic Cells Undergo Myogenic Differentiation Following a Pax-7 Independent Pathway

“…MyoD independence of the process can be explained by its well-known redundancy with Myf5 [46]. Pax7 independence, appears to contradict our hypothesis of a stepwise myogenic differentiation of hematopoietic cells, owing to the central role that Pax7 has in myoblast proliferation and self-renewal [33][34][35][36]. Furthermore, it is opposing with the Pax7-dependent myogenic specification suggested by Seale and coworkers [33,37].…”

“…Pax7 belongs to the paired box family of transcription factors and is expressed in satellite cells and proliferating myoblasts. Initially thought to be necessary for the myogenic specification of the satellite cells [33], it was proven by later studies to be essential for the propagation and the maintenance of the satellite cells via its antiapoptotic activity [34][35][36].…”