An overview of phrenic nerve and diaphragm muscle development in the perinatal rat

In this overview, we outline what is known regarding the key developmental stages of phrenic nerve and diaphragm formation in perinatal rats. These de velopmental events include the following. Cervical axons emerge from the sp inal cord during embryonic (E) day 11. At similar to E12.5, phrenic and bra chial axons from the cervical segments merge at the brachial plexi. Subsequ ently, the two populations diverge as phrenic axons continue to grow ventra lly toward the diaphragmatic primordium and brachial axons turn laterally t o grow into the limb bud. A few pioneer axons extend ahead of the majority of the phrenic axonal population and migrate along a well-defined track tow ard the primordial diaphragm, which they reach by E13.5. The primordial dia phragmatic muscle arises from the pleuroperitoneal fold, a triangular protr usion of the body wall composed of the fusion of the primordial pleuroperit oneal and pleuropericardial tissues. The phrenic nerve initiates branching within the diaphragm at similar to E14, when myoblasts in the region of con tact with the phrenic nerve begin to fuse and form distinct primary myotube s. As the nerve migrates through the various sectors of the diaphragm, myob lasts along the nerve's path begin to fuse and form additional myotubes. Th e phrenic nerve intramuscular branching and concomitant diaphragmatic myotu be formation continue to progress up until E17, at which time the mature pa ttern of innervation and muscle architecture are approximated. E17 is also the time of the commencement of inspiratory drive transmission to phrenic m otoneurons (PMNs) and the arrival of phrenic afferents to the motoneuron po ol. During the period spanning from E17 to birth (gestation period of simil ar to 21 days), there is dramatic change in PMN morphology as the dendritic branching is rearranged into the rostrocaudal bundling characteristic of m ature PMNs. This period is also a time of significant changes in PMN passiv e membrane properties, action-potential characteristics, and firing propert ies.