Dynamic patterns of mononucleated myogenic cell populations in the developing rat hindlimb.

ABSTRACT

Formation of an organ is governed by both the genetic programming of individual cells and dynamic interactions amongst different cell communities or the 'community effect'. Using the developing vertebrate limb muscle, we identified myogenic stem cell communities derived from migratory somitic cells. These cells express Pax3, a gene from the paired box (PAX) family of transcription factors and Pax7, a paralog of Pax3. Both Pax genes act upstream of myogenic regulatory factor (MRF) whose activation marks a specified myogenic lineage and subsequent differentiation. Quantitative analyses on the size of the individual cell populations revealed that Pax3 and MRF compartments remained constant. Further analysis showed that the size of the Pax7 cell population increased significantly. The pool of foetal MRF populations contained decreasing Pax3 and increasing Pax7 proportions. This increase is dynamic at the developmental stage. Upon abrupt disruption of the p38 regulatory pathway for myogenic differentiation, established kinetic patterns were significantly altered. Changes in the proportions of these myogenic subpopulations imply that a community effect involving dynamic interactions among differentiating cell communities may play a crucial role in correct maintenance and propagation of myogenic stem cells.