Role of nerve and muscle factors in the development of rat muscle spindles

Abstract

The soleus muscles of fetal rats were examined by electron microscopy to determine whether the early differentiation of muscle spindles is dependent upon sensory innervation, motor innervation, or both. Simple unencapsulated afferent-muscle contacts were observed on the primary myotubes at 17 and 18 days of gestation. Spindles, encapsulations of muscle fibers innervated by afferents, could be recognized early on day 18 of gestation. The full complement of spindles in the soleus muscle was present at day 19, in the region of the neuromuscular hilum. More afferents innervated spindles at days 18 and 19 of gestation than at subsequent developmental stages, or in adult rats; hence, competition for available myotubes may exist among afferents early in development. Some of the myotubes that gave rise to the first intrafusal (bag2) fiber had been innervated by skeletomotor (alpha) axons prior to their incorporation into spindles. However, encapsulated intrafusal fibers received no motor innervation until fusimotor (gamma) axons innervated spindles 3 days after the arrival of afferents and formation of spindles, at day 20. The second (bag1) intrafusal fiber was already formed when gamma axons arrived. Thus, the assembly of bag1 and bag2 intrafusal fibers occurs in the presence of sensory but not gamma motor innervation. However, transient innervation of future bag2 fibers by alpha axons suggests that both sensory and alpha motor neurons may influence the initial stages of bag2 fiber assembly. The confinement of nascent spindles to a localized region of the developing muscle and the limited number of spindles in developing muscles in spite of an abundance of afferents raise the possibility that afferents interact with a special population of undifferentiated myotubes to form intrafusal fibers.

Target‐determined expression of α3 isoform of the Na+,K+‐ATPase in the somatic nervous system of rat

“…Differentiation of the myotubes into intrafusal muscle fibers is associated with the invasion of the limb bud by growing axons and contact of myotybes by the Ia afferents (E18 -19). Secondary afferents innervate muscle spindles about 1 day later (E19 -20), and finally the efferents innervate the intrafusal muscle fibers at E20 -21 (Kucera et al, 1988(Kucera et al, , 1989Copray and Brouwer, 1994). The full morphological and functional development of the rat hindlimb muscle spindles is achieved during the first 2 postnatal weeks, when the adult complement of four to five intrafusal fibers per spindle and all components of mature stretch reflex are present Yamada, 1985, 1987;Kucera et al, 1988Kucera et al, , 1989Copray and Brouwer, 1994;Sharabani-Yosef et al, 1999).…”

“…The day of appearance of sperm from vaginal swabs was designated as day 0 of gestation (Kucera et al, 1989). On gestational days 15, 17, 19, or 21 the rats were anesthetized with sodium pentobarbital (55 mg/kg), the fetuses removed, placed in ice-cold buffer solution, and then euthanized by decapitation.…”

“…The third expectation is that denervation and loss of neurotrophic support from the target is likely to result in a decrease in the number of ␣ 3 Na ϩ ,K ϩ -ATPase peripheral neurons. The structure and innervation of muscle spindles is well studied in developing and adult vertebrate animals, both under control conditions and after axotomy (Barker et al, 1985;Kucera et al, 1988Kucera et al, , 1989Banks, 1994;Rees et al, 1994;Oakley et al, 1995). However, previous studies on the expression of ␣ 3 Na ϩ ,K ϩ -ATPase in vertebrates were mostly limited to evaluation of tissues of normal adult rats, providing no insight into the expression of this isoform during development or in animal models of axotomy (Mata et al, 1993;Zahler et al, 1996;Gerbi et al, 1999;Dobretsov et al, 1999bDobretsov et al, , 2003.…”

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).…”

Differential sensitivity of skeletal and fusimotor neurons to Bcl-2-mediated apoptosis during neuromuscular development

“…25 Initially, both neural types make similar innervations to primary myofibers. 26 A primary difference between these two motor classes relates to the temporal pattern of their differentiation. 27 The majority of motor neurons differentiate during the early phase of spinal cord development (embryonic day 10-11 in rodents), and primary motor neurogenesis is essentially complete by E14.…”