Genetic specification and lifespan development

This chapter deals with the embryonic, perinatal, and postnatal development of the neuromuscular system and its decline in old age. The concentration of sonic hedgehog protein has a crucial role in the molecular specification of future motoneurones within the embryonic neural tube. At a later stage, many (e.g., about half) of the developing motoneurones will die (programmed cell death), apparently in the course of competition for connections to peripheral target cells in developing muscle tissue. At this stage, myoblasts are already fusing to form different generations of myotubes and, particularly for later myotube generations, motoneuronal innervation is important for their further differentiation to muscle fibres. Initially single muscle fibres receive a poly-neuronal innervation, and differentiation into the adult mono-neuronal pattern partly takes place under the influence of motoneuronal activity. In old age, muscles become thinner and weaker, apparently partly due to death of (large) motoneurones.