Key aspects of phrenic motoneuron and diaphragm muscle development during the perinatal period

Abstract

At the time of birth, respiratory muscles must be activated to sustain ventilation. The perinatal development of respiratory motor units (comprising an individual motoneuron and the muscle fibers it innervates) shows remarkable features that enable mammals to transition from in utero conditions to the air environment in which the remainder of their life will occur. In addition, significant postnatal maturation is necessary to provide for the range of motor behaviors necessary during breathing, swallowing, and speech. As the main inspiratory muscle, the diaphragm muscle (and the phrenic motoneurons that innervate it) plays a key role in accomplishing these behaviors. Considerable diversity exists across diaphragm motor units, but the determinant factors for this diversity are unknown. In recent years, the mechanisms underlying the development of respiratory motor units have received great attention, and this knowledge may provide the opportunity to design appropriate interventions for the treatment of respiratory disease not only in the perinatal period but likely also in the adult.

Fig. 1

Schematic showing the timeline for major events in the development of the rat diaphragm muscle (DIAm). Similar key events occur in other mammals, including humans, during the perinatal development of DIAm motor units. However, temporal characteristics and interrelationships may vary. E and P refer to embryological and postnatal days, respectively.

Fig. 2

Schematic showing the timeline for major events in the development of rat DIAm motor units. MHC, myosin heavy chain.

Fig. 3

Confocal photomicrographs displaying phrenic motoneurons that were retrogradely labeled by DIAm injection of cholera toxin B-fragment. Motoneurons are shown at postnatal day 10 (P10, A and B) and in the adult rat (C). Neurolucida camera tracings are shown in D and E for P10 and adult motoneurons, respectively. Note differences in cell size (B and C) and dendritic arborization (D and E). Bar indicates 200 μm (A) and 50 μm (B and C).

Fig. 4

Timeline of changes in DIAm mass (A), DIAm fiber cross-sectional area (B), and DIAm fiber length (C). Data are means ± SE, summarized from published reports (32, 91, 107).