Specific pattern of cell cycle during limb fetal myogenesis

Area of Science:

• Developmental Biology
• Cell Biology
• Muscle Development

Background:

• Precise control of cell proliferation and differentiation is crucial for organismal growth.
• The signals governing cell proliferation in vivo remain incompletely understood.

Purpose of the Study:

• To investigate the spatial distribution and cell cycle status of proliferating cells in developing mouse limbs.
• To characterize the cell cycle behavior of myogenic cells during fetal development and in adult cultures.

Main Methods:

• Utilized the Fluorescent ubiquitynation-based cell-cycle indicator (Fucci) system for real-time cell cycle visualization.
• Employed retroviral RCAS system for Fucci cassette expression in chick embryos.
• Analyzed cell cycle states of myogenic cells in fetal muscles, adult myoblast cultures, and isolated muscle fibers using Fucci transgenic mice.

Main Results:

• Terminally differentiated myonuclei consistently displayed red fluorescence (G1 phase) in fetal and adult muscle tissues (in vivo, ex vivo, and in vitro).
• Muscle progenitors and myoblasts in G1 phase were not fully captured by the Fucci system.
• Pax7+ cells in fetal mouse myogenesis were predominantly in S/G2/M phases, exhibiting a distinct pattern delineating muscles and accumulating at muscle tips.

Conclusions:

• Myonuclei exit the cell cycle in G1 phase and maintain a stable G1-like state.
• Proliferating cells (Pax7+) in fetal limbs show spatial regionalization, concentrating at muscle borders and the muscle-tendon interface.
• The Fucci system provides insights into cell cycle dynamics during myogenesis, highlighting specific patterns of proliferation in developing muscles.