Innervation of developing intrafusal muscle fibers in the rat

Abstract

The chronology of development of spindle neural elements was examined by electron microscopy in fetal and neonatal rats. The three types of intrafusal muscle fiber of spindles from the soleus muscle acquired sensory and motor innervation in the same sequence as they formed--bag2, bag1, and chain. Both the primary and secondary afferents contacted developing spindles before day 20 of gestation. Sensory endings were present on myoblasts, myotubes, and myofibers in all intrafusal bundles regardless of age. The basic features of the sensory innervation--first-order branching of the parent axon, separation of the primary and secondary sensory regions, and location of both primary and secondary endings beneath the basal lamina of the intrafusal fibers--were all established by the fourth postnatal day. Cross-terminals, sensory terminals shared by more than one intrafusal fiber, were more numerous at all developmental stages than in mature spindles. No afferents to immature spindles were supernumerary, and no sensory axons appeared to retract from terminations on intrafusal fibers. The earliest motor axons contacted spindles on the 20th day of gestation or shortly afterward. More motor axons supplied the immature spindles, and a greater number of axon terminals were visible at immature intrafusal motor endings than in adult spindles; hence, retraction of supernumerary motor axons accompanies maturation of the fusimotor system analogous to that observed during the maturation of the skeletomotor system. Motor endings were observed only on the relatively mature myofibers; intrafusal myoblasts and myotubes lacked motor innervation in all age groups. This independence of the early stages of intrafusal fiber assembly from motor innervation may reflect a special inherent myogenic potential of intrafusal myotubes or may stem from the innervation of spindles by sensory axons.

The Generation of Neuronal Heterogeneity in a Rat Sensory Ganglion

“…DiI injection and growthassociated protein-43 immunolabeling indicates some sensory afferents in the epidermis of the proximal hindlimb quite early, around E14, and some fibers reach the paw by E14.5-E15 (Reynolds et al, 1991;Coggeshall et al, 1994;Mirnics and Koerber, 1995), but it is not possible to quantify their prevalence. Physiological assays indicate that the first afferent terminals are formed later, at E17-E18 in hindlimb muscles (Kudo and Yamada, 1985;Kucera et al, 1988Kucera et al, , 1989, and cutaneous plantar reflexes appear at E17.5 (Kudo and Yamada, 1985). It is unlikely that neurons have been influenced by cutaneous targets, because epidermis does not differentiate until E15-E17 (Kopan and Fuchs, 1989).…”

“…Cutaneous afferents appear in rat proximal hindlimb on embryonic days 14 -15 (E14 -E15) and in skin of distal toes at E16 -E17 (Reynolds et al, 1991;Mirnics and Koerber, 1995). These fibers are functional slightly later, beginning at E17 (Saito, 1979;Kudo and Yamada, 1985;Fitzgerald, 1987;Kucera et al, 1988;Fitzgerald, 1991). Neuropeptides appear around the time of peripheral target functional contacts (E18 -E19) (Kessler and Black, 1981;Senba et al, 1982), suggesting that target interactions could influence sensory neuronal phenotype.…”

Skeletal fiber types and spindle distribution in limb and jaw muscles of the adult and neonatal opossum,Monodelphis domestica

“…However, in rat muscle, the first contact between primary myotubes and invading afferent axons (which initiates spindle formation; Kucera et al, 1988) is followed very shortly afterward by expression of tonic myosin in presumptive bag2 fibers Kucera et al, 1993). Our immunostaining identified spindles at this early stage throughout the thoracic and forelimb muscles of Monodelphis neonates, and we expect that it would also reveal developing spindles in M. eugenii at birth, especially because the organisation of dorsal root ganglia and dorsal horn neurons supplying these muscles was reported to be well advanced.…”

Depolarization Stimulates Initial Calcitonin Gene-Related Peptide Expression by Embryonic Sensory NeuronsIn Vitro

“…CGRP is localized in polymodal nociceptors and is a potent vasodilator (Brain et al, 1985;Wallengren and Hakanson, 1987;Holzer, 1988;Scott, 1992). Although CGRP first appears in lumbar DRG in vivo when peripheral target connections are functional on embryonic day 18 (E18) (Narayanan et al, 1971;Saito, 1979;Kudo and Yamada, 1985;Marti et al, 1987;Kucera et al, 1988;Fitzgerald, 1991), cell culture studies with E14 rat DRG indicate that de novo CGRP expression occurs in the absence of those target contacts (Hall et al, 1997). Transcription and steady-state CGRP mRNA levels in cell lines can be upregulated by cAM P, forskolin, phorbol ester, and nerve growth factor or can be inhibited by glucocorticoids, retinoic acid, and vitamin D (deBustros et al, 1985(deBustros et al, , 1986Haller-Brem et al, 1988;NavehMany and Silver, 1988;Lindsay and Harmar, 1989;Russo et al, 1992;T verberg and Russo, 1992).…”