Trophic factor expression in phrenic motor neurons

Abstract

The function of a motor neuron and the muscle fibers it innervates (i.e., a motor unit) determines neuromotor output. Unlike other skeletal muscles, respiratory muscles (e.g., the diaphragm, DIAm) must function from birth onwards in sustaining ventilation. DIAm motor units are capable of both ventilatory and non-ventilatory behaviors, including expulsive behaviors important for airway clearance. There is significant diversity in motor unit properties across different types of motor units in the DIAm. The mechanisms underlying the development and maintenance of motor unit diversity in respiratory muscles (including the DIAm) are not well understood. Recent studies suggest that trophic factor influences contribute to this diversity. Remarkably little is known about the expression of trophic factors and their receptors in phrenic motor neurons. This review will focus on the contribution of trophic factors to the establishment and maintenance of motor unit diversity in the DIAm, during development and in response to injury or disease.

Figure 1

Schematic representation of a motor unit (i.e., a motoneuron and the muscle fibers it innervates) and the potential sources of trophic factor influence on motor units. Trophic factors and their receptors (in italics) are noted for each source. A ? sign is used if expression at that site is not reported consistently. *, denotes expression mainly following injury or disease. Parentheses indicate expression by only a subset of motor neurons. See text for details. BDNF, brain-derived neurotrophic factor; GDNF, glial cell line-derived neurotrophic factor; GFR, GDNF family receptor; NRG, neuregulin; NT, neurotrophin; p75^NTR, p75 neurotrophin receptor; RET, rearranged in transfection receptor; Trk, tropomyosin-related kinase receptor.